Hirshberg Foundation 2013 Winter Newsletter

FOUNDATION NEWSLETTER WINTER 2013–2014

HIRSHBERG FOUNDATION FOR PANCREATIC CANCER RESEARCH

Anirban Maitra, MD – Pg. 5

Gabriela Chiosis,PhD – Pg. 9

David Gius, PhD, MD – Pg. 5

Celebrating 10 Years of Hirshberg Seed Grants

IN THIS ISSUE 3 — Agi's Message

LA CANCER CHALLENGE

4 — APA Meeting Overview 4 — Agi Hirshberg Receives APA Distinguished Service Award

22 — 16th Annual LACC Recap

31 — 30 Days to Shine a Light on a Year Round Battle

24 — The Dedolians 24 — Chuyera

APA / HIRSHBERG SYMPOSIUM PRESENTATIONS

25 — Martin's Marchers 25 — Team Guayas

5 — Anirban Maitra, MD - UT MD Anderson Cancer Center 5 — David Guis, MD, PhD - Northwestern University

26 — Team Adam Zauder 27 — Team LANA

6 — Isidore Rigoutsos, Phd - Thomas Jefferson University

28 — Ohana Means Family

9 — Ashok K. Saluja, PhD - University of Minnesota

28 — Sandford Family

9 — Gabriela Chiosis, PhD - Memorial Sloan-Kettering Cancer Center 10 — Parkash Gill, MD - USC Norris Cancer Center

29 — Milstein Adelman 29 — Mia's Angels

10 — Alexandros Tzatsos, MD, PhD - Massachusetts General Hospital Cancer Center

30 — Maggie's First 5K

11 — Diane M. Simeone, MD - University of Michigan 11 — Mouad Edderkaoui, PhD - Cedars-Sinai Medical Center & University of California, Los Angeles

DIRECTORS & TRUSTEES

12 — Kathleen Hertzer, MD, PhD - University of Californa, Los Angeles 12 — Vay Liang W. Go, MD - University of California, Los Angeles 13 — David Wond, DMD, DMsc - Univeristy of California, Los Angeles To view the complete presentations, including slide shows and videos, please visit www.Pancreatic.org

WINNERS OF THE HIRSHBERG AWARD FOR BEST ABSTRACT 7 — Noboru Ideno, PhD - Kyushu University, Fukuoka, Japan 8 — Junpei Yamaguchi, MD, PhD - Massachusetts General Hospital & Harvard Medical School

Agi Hirshberg, President & Founder Lisa Manheim, Director Stephen C. Prince, CPA - Treasurer Michael Scott, Esq. - Secretary Jon Hirshberg, Trustee Lisa Hirshberg, Trustee Michael Berliner, Trustee SCIENTIFIC ADVISORY BOARD Vay Liang W. Go, MD, Chair Laszlo G. Boros, MD Murray Korc, MD

EVENTS

Anirban Maitra, MD Laurence J. Miller, MD

14 — Inspiring Hope & Engaging Your Community

Stephen J. Pandol, MD

15 — How to Tee-Off Your First Event

Howard A. Reber, MD Lee S. Rosen, MD

16 — The Canyon Salon's 2nd Annual Style-A-Thon

Ashok K. Saluja, PhD

17 — 3rd Annual Julie Durmaskin Memorial Game Day 18 — Fishing For a Cure: The Larry Meister Memorial Trout & Bass Tournament 19 — Special Events Calendar 2014

Diane M. Simeone, MD HIRSHBERG FOUNDATION FOR PANCREATIC CANCER RESEARCH 2990 S. SEPULVEDA BLVD. , SUITE 300C

MAKING A DIFFERENCE

LOS ANGELES, CA 90064 (310) 473-5121 (P) — (310) 473-5107 (F)

20 — Going the Extra Mile for Families Impacted by Pancreatic Cancer 21 — Pants Off Racing, Inc. — Adopt-A-Family Program

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WWW.PANCREATIC.ORG

WELCOME

A Year at a Glance With this issue, we pause and reflect on a year of progress in research, programming and fundraising. Most importantly, we stop to recognize the families who are committing their time and skills to advance our goal of a cure.

Agi, Jon and Lisa at LACC

While looking back on 2013, I can’t help but ask myself - Did we help enough patients? Did we offer solace to families? Did we communicate with you enough? Did we fund the right research projects and did we achieve progress in improving treatments? I am pleased to be able to answer each question with an enthusiastic “yes!” To my amazement, the speed of research is escalating with more private funding, with improved computer technologies and with new insights from the fields of genomics, proteomics and metabolomics.

Allow me to summarize the year at a glance, as I see it. • Minnelide, a new drug treatment, is now in clinical trials. The first steps will assess proper dosage and safety in patients. • Metformin, an anti-diabetic drug, is in clinical trials in 59 locations worldwide. Despite this drug having been approved for safety 35 years ago, current testing now involves inhibiting cancer cell growth. • Abraxane was approved by the FDA after many years of clinical trials and the drug is now extending life by several months or years for many patients. • For early diagnosis, the non-invasive salivary test – conducted in a dental office – continues to show promise in the detection of pancreatic cancer. Expanded studies are now supported by the NIH. • For prevention, our research funding continues to emphasize diets that can prevent cancers, as fructose is an important culprit in tumor growth. Obesity and Type 2 diabetes account for the startling projection that, by the year 2020, pancreatic cancer will be the second leading cause of cancer related deaths. • For treatment options, mechanism of action (discovering which cells interact with other cells) remains forefront in our research efforts, in order to support the development of new effective targeted treatments. Looking back at the years’ progress, I am proud of what we have accomplished. Yet despite all of this, we must recognize that the number of patients being diagnosed has increased to 45,000, which means we must do more! We know that continuing to fund promising research will change the outcome of the diagnosis, as it has for other cancers. As we look ahead to 2014, we hope you will continue to be part of our progress. Thank you for all that you have done to support our efforts, and for all that you will continue to do.

Warmly,

Agi Hirshberg, President and Founder WWW.PANCREATIC.ORG

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APA MEETING OVERVIEW

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he 10th Agi Hirshberg Symposium was held in conjunction with the 44th annual meeting of the American Pancreatic Association in Miami from October 30 - November 2, 2013. The program highlighted a decade of achievements of the Hirshberg Foundation Seed Grant Program. All former seed grant awardees, both nationally and internationally, were invited to participate. Martin Freeman, MD, President of the American Pancreatic Association, remarked “Agi Hirshberg has been a longtime friend of APA, not to mention the entire pancreas community. Helping her celebrate the 10th Anniversary of the Hirshberg Seed Grant Program is an honor.”

APA/Hirshberg

SYmpoSium

Celebrating 10 Years of the Hirshberg Seed Grant November 2, 2013 Eden Roc Hotel • Miami, Florida

Dr. Vay Liang Go, Chair of the Hirshberg Foundation’s Scientific Advisory Board, said “The board is very pleased and proud of the achievements of the program to date. We were honored to attend this national celebration and congratulate the Hirshberg Foundation for the success of their research seed grant program.”

pancreatic cancer, and pancreatitis. The Abstract Poster Presentations allowed authors to showcase their research in poster format. Those authors of abstracts selected as posters of distinction each gave a 3-minute talk highlighting their research during the morning poster time. Drawing an international audience, the meeting planners received nearly 250 abstracts from 21 different countries.

In addition to the Hirshberg Symposium, the 400 participants at the APA Meeting listened to state-of-the-art lectures and attended mini-symposia. The Scientific/Abstract Sessions addressed basic and clinical science issues in basic science,

The meeting also included the presentation of the Hirshberg Award for Best Abstracts in Pancreatic Cancer. The awards were presented to Noboru Ideno, Kyushu University and Junpei Yamaguchi, Massachusetts General Hospital.

AGI HIRSHBERG RECEIVES APA DISTINGUISHED SERVICE AWARD

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he Governing Board of the APA honored Agi Hirshberg as the recipient of their Distinguished Service Award. Chosen for her unyielding dedication to the pancreatic cancer scientific community, Hirshberg was the first nonmedical recipient of the award. Hirshberg commented, “I am extremely proud that our foundation’s significant contribution and commitment toward advances for pancreatic cancer was recognized by the

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American Pancreatic Association this year. I was honored to receive this award, which reflects our commitment to the pancreatic cancer patient community and an ongoing pledge to provide funding for pancreatic cancer research through our seed grant program.” Dr. Vay Liang Go, one of the cofounders of the APA and Chair of the Hirshberg Foundation Scientific Advisory Board credited Hirshberg for her “vision, leadership, and stewardship in pancreatic cancer research” and noted that the Hirshberg Foundation’s seed grant program has led to over $45 million in additional funding from the National Institutes of Health (NIH) and other funding agencies. At the meeting, the APA also recognized the 10th Anniversary of the seed grant program during the APA/Hirshberg Symposium.

YOU CAN HOPE OR YOU CAN HELP®

APA/HIRSHBERG SYMPOSIUM: CELEBRATING 10 YEARS OF THE HIRSHBERG SEED GRANT

Pancreatic Cancer—Making Mountains out of Genomic Molehills ANIRBAN MAITRA, MD UT MD ANDERSON CANCER CENTER

The sequencing of the pancreatic cancer genome has identified somatic mutations of KRAS as the most preponderant alteration in this neoplasm, but unlike lung cancer or melanomas, no major subsets have emerged in terms of actionable mutations. Therapeutic targeting of mutant KRAS per se has not been successful in the clinic, although significant research efforts are underway to develop novel targeting strategies, including a concerted federally funded project at the NCI. In the interim, blocking proximate downstream effectors of oncogenic KRAS, particularly as combination therapies to account for compensatory pathway activation, remains a tractable choice that is being explored in the clinic. While mutant KRAS remains the big “enchilada” in pancreatic cancer, parsing the genomic data does identify

other minor subsets (“genomic molehills”) with potential for therapeutic intervention. The best cited example is biallelic loss of function mutations of the Fanconi anemia genes, which render the neoplastic cells exquisitely sensitive to PARP inhibitors or platinum agents. Other minor subsets include tumors with activating mutations of ERBB2, tumors that are wild-type for KRAS, and those with alterations of the PIK3CA pathway. Given the relative infrequency of these alterations, it is unlikely that one can conduct pancreatic cancer-centric clinical trials that would require apriori documentation of any given somatic mutation. Instead, a more pragmatic approach might be to conduct “basket” trials that are tumor agnostic and enroll by mutational profile. An unexplored dimension in pancreatic cancer pertains to the significant subset (25-30%) of tumors that harbor loss of function mutations of chromatin modifying genes, such as MLL3, MLL2, ARID1A, KDM2B, etc. Genetically engineered models recapitulating these mutations should provide a platform for co-clinical trials, in order to identify therapeutic targets that are synthetic lethal to these loss of function mutations.

Acetylation of Mutant KRAS Lysine 147 is an Oncogenic Post–Translation Modification Directed by SIRT2

DAVID GIUS, MD, PHD NORTHWESTERN UNIVERSITY

KRAS activating mutations are present in up to thirty-five percent of lung a d e n o c arc i n om a s ; however, as is observed in other human malignancies, additional aberrant genetic and/or biochemical events are required for carcinogenesis. In addition, it has been shown that mtKRAS activity in lung cancer cells, whether mouse or human, is highly elevated, as compared with adjacent, untransformed cells with similar mutant KRAS levels. WWW.PANCREATIC.ORG

These observations point to the importance of mtKRAS enzymatic activity in lung and pancreas adenocarcinoma and imply that modulating enzymatic activity influences carcinogenesis. Thus, our results suggest that cells lacking Sirt2, or exhibiting decreased SIRT2 activity, will have increased aberrant mtKRAS acetylation and enzymatic activity and this plays a role in the establishment of an adenocarcinomas permissive phenotype. A significant percentage of human lung and pancreas adenocarcinomas contain mutant KRAS (mtKRAS) protein and mice lacking Sirt2 develop lung adenocarcinomas suggesting a potential mechanistic oncogenic connection. SIRT2 interacts with, continued on next page

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APA/HIRSHBERG SYMPOSIUM: CELEBRATING 10 YEARS OF THE HIRSHBERG SEED GRANT continued on previous page deacetylates, and directs mtKRAS enzymatic activity. Mass spectrometry and an anti-KRASAc-K147 antibody showed that SIRT2 deacetylates KRAS lysine 147, and a substitution mutant (KRASG12D to KRASG12D-K147Q) that mimics an acetylated lysine, exhibited increased enzymatic activity and a more in vitro transformed phenotype. Sir2-/--KRASG12D mice exhibited lung and pancreas tumors earlier than the

KRASG12D mice. Finally, anti-KRAS-Ac-K147 antibody staining tumors showed increased mtKRAS acetylation in the murine Sirt2-/--KRASG12D and KRASLSL tumors and human lung and pancreas adenocarcinomas samples. These results suggest that mtKRAS contains a potential oncogenic acetyl-lysine post-translation-modification.

The Increasingly Important Roles of Post-Transcriptional Regulation in Pancreatic Cancer ISIDORE RIGOUTSOS, PHD THOMAS JEFFERSON UNIVERSITY

Pancreatic cancer remains one of the most lethal types of cancer in spite of tremendous progress in elucidating the molecular events of pancreatic tumorigenesis. Over the years, research efforts focused largely on the genetic aspects of the disease. By comparison, the contributions beyond genetic and transcriptional events remained underexplored. MicroRNAs (miRNAs) are short non-coding RNAs (ncRNAs) approximately 22 nts in length that are potent mediators of post-transcriptional regulation. MiRNAs target messenger RNAs (mRNAs) in their untranslated and amino acid coding regions in a sequence-dependent manner. MiRNAs also bind pseudogenes and other ncRNAs. Posttranscriptional regulation by miRNAs exhibits tissue- and cell-state-dependent characteristics and is critical to many fundamental biological processes. Links to miRNAs have been demonstrated in development, neurodegeneration, immunity, aging, many cancers, etc. Consequently, “signatures” composed of dysregulated miRNAs have been

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determined for many of these contexts including pancreatic cancer. We and others have been generating evidence for several years, in both human and mouse, that the “canonical model” of miRNA targeting is incomplete and that a far more complex “expanded model” is at work: according to the latter, miRNAs regulate many more genes than originally believed and do so through more complex and intricate interactions. Recent technological and methodological advances now make it possible to begin improving our mechanistic understanding of the rules that govern miRNA regulation of the transcriptome in pancreatic cancer, and in other settings. Using a combination of newly developed computational methods and Ago CLIP-seq (=deep sequencing of RNA after UV cross-linking and immunoprecipitation with an Ago antibody) in pancreatic cancer cell lines, we uncovered unexpected facets of miRNA activity with far-reaching implications about the roles of miRNAs. Our findings confirm that the “expanded model” is in effect in pancreatic cancer cells and provide a solid foundation for an in-depth exploration of these post-transcriptional aspects of the disease process and their relationships to chemotherapeutic efficacy and resistance mechanisms.

YOU CAN HOPE OR YOU CAN HELP®

APA/HIRSHBERG SYMPOSIUM: CELEBRATING 10 YEARS OF THE HIRSHBERG SEED GRANT WINNER OF THE HIRSHBERG AWARD FOR BEST ABSTRACT IN PANCREATIC CANCER

Clinical significance of GNAS mutation for invasive pancreatic carcinoma distinct from/derived from intraductal papillary mucinous neoplasm (IPMN) of the pancreas. NOBORU IDENO, PHD KYUSHU UNIVERSITY, FUKUOKA, JAPAN

Background: Although GNAS mutations are specific for IPMN, IPMN without GNAS mutation has not been well characterized. The aims of this study were to investigate the GNAS mutational status in IPMN with and without distinct pancreatic ductal adenocarcinoma (PDAC) and IPMN with an associated invasive carcinoma and to evaluate the significance of GNAS mutation analysis of duodenal fluid (DF) in patients with IPMN. Methods: Clinicopathologic features of 62 patients with IPMN including 18 with distinct PDAC and 20 with IPMN with an associated invasive carcinoma were reviewed. GNAS mutational status of the tissue samples was assessed by cycle sequencing, high-resolution-melt-curve analysis, and competitive allele specific TaqMan PCR (cast PCR). DF samples were available in 24 patients, and GNAS mutation in DF was investigated by cast PCR. Results: The rate of GNAS mutations in IPMN with distinct PDAC was significantly lower than that in IPMN without PDAC (5/18, 28% vs 19/24, 79%, P=0.002). By multivariate analysis, the absence of GNAS mutation reached statistical significance as an independent predictor of the presence of distinct PDAC (P=0.018). GNAS mutations were not detected in 12 of 20 IPMNs with associated invasive carcinomas (60%). In DF samples, GNAS mutations were found in 11 of 24 (46%) samples, and the mutant status was consistent with that of tissue samples in 22 of 24 (92%). Of note, in 13 patients whose DF exhibited no GNAS mutation, 5 (38%) had PDAC concomitant with IPMN, and 3 (23%) had IPMN with an associated invasive carcinoma. Conclusions: The absence of GNAS mutations might be a predictor for the development of invasive pancreatic carcinoma distinct from IPMN, and mutational analysis of GNAS using DF might be clinically useful for the selection of high risk patients.

WWW.PANCREATIC.ORG

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APA/HIRSHBERG SYMPOSIUM: CELEBRATING 10 YEARS OF THE HIRSHBERG SEED GRANT WINNER OF THE HIRSHBERG AWARD FOR BEST ABSTRACT IN PANCREATIC CANCER

Loss of TFF2 in Pancreatic Duct Glands (PDG) results in the formation of IPMN suggesting TFF2 may function as a tumor suppressor. JUNPEI YAMAGUCHI, MD, PHD MASSACHUSETTS GENERAL HOSPITAL AND HARVARD MEDICAL SCHOOL

Background: PDG are a novel epithelial progenitor compartment important for regeneration of the ductal epithelium. Our early correlative studies suggest that dysregulation of this compartment may result in formation of IPMN. This compartment uniquely expresses trefoil family factor 2 (TFF2). PDG functionally and molecularly resemble gastric glands. In the stomach TFF2 has been reported to be the tumor suppressor of gastric cancer, suggesting that TFF2 also act as the tumor suppressor to prevent the initiation of pancreatic mucinous neoplasms. Methods: In vivo TFF2-knockout mice (TFF2-KO) were bred to generate TFF2KO;Pdx-Cre;LSL-KRASG12D, which were harvested at 2, 4 and 6 months then histologically evaluated. In vitro a pancreatic cancer cell line (Panc-1) was transfected with a TFF2-overexpressing vector to evaluate the impact of TFF2 on proliferation. Results: In the pancreas of KRASG12D and TFF2-KO mice, no neoplastic epithelium was identified at 2, 4 and 6 months old. The absence of TFF2 in combination with the background of activated KRASG12D mutation results not only in expansion of PDG compartment, but also in the formation of intraductal papillary mucinous neoplasms (IPMN) predominantly of the main pancreatic duct by 2 month. High to moderate grade IPMN were identified by 4-6 months. In vitro the induction of TFF2-expression in cancer cell line resulted in a decrease in proliferation. TFF2 over expression and its effect on proliferation was associated with an increase in nuclear SMAD4. Conclusion: TFF2 act as the tumor suppressor in PDG. This effect may be mediated by its effect on SMAD 4.

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APA/HIRSHBERG SYMPOSIUM: CELEBRATING 10 YEARS OF THE HIRSHBERG SEED GRANT

An emerging novel therapy against pancreatic cancer: Minnelide ASHOK K. SALUJA, PHD UNIVERSITY OF MINNESOTA

Pancreatic cancer is one of the most lethal human malignancies, with an all-stage 5-year survival of <5%, a number that highlights the urgent need for more effective therapeutic strategies. Our studies have shown that triptolide, a diterpenoid, is effective against pancreatic cancer cells in vitro as well as in vivo. However, triptolide is poorly soluble in water, limiting its clinical utility. We have recently synthesized a water-soluble prodrug of triptolide, Minnelide that has shown tremendous promise in preclinical studies. Our studies have shown that triptolide induces ER stress and inhibits NF-kB, thereby affecting two pathways that play a prominent role in carcinogenesis. Furthermore, our data suggest that triptolide affects these two pathways

by downregulating Specificity protein1 (Sp1). Sp1 is a transcription factor that is not expressed in terminally differentiated pancreatic cells but is overexpressed in pancreatic cancer cell lines. Both NF-kB and ER stress proteins are regulated by transcriptional activity of Sp1. Triptolide inhibits the activity of Sp1 leading to downregulation of NF-kB on one hand and induction of ER stress on the other hand. This leads to downregulation of heat shock proteins and results in lysosomal membrane permeabilization, which culminates in cell death Our study shows for the first time that triptolide-induced cell death in pancreatic cancer is mediated by down regulation of pro-survival pathways (like ER stress, HSP70 and NF-kB) controlled by Sp1. This molecular analysis of the mode of action of triptolide or Minnelide is of great usefulness in delineating its biological function as it is undergoing Phase 1 clinical trials since August 2013.

Insights into the translation of HSP inhibitors to the treatment of pancreatic cancer

GABRIELA CHIOSIS, PHD MEMORIAL SLOAN-KETTERING CANCER CENTER

The development of a malignant phenotype is associated with dysregulation of multiple pathways and molecules. To adapt, cells co-opt heat shock proteins (HSPs) to help maintain a functional cellular state under the transforming pressure. Among the major HSPs are Hsp90 and Hsp70, proteins that act in an interconnected but also distinct fashion to regulate and maintain the disease phenotype. In pancreatic cancer, these HSPs have a major role in maintaining the altered signaling pathways and the elevated anti-apoptotic threshold characteristic of these tumors. Consequently, approaches that target these HSPs are especially promising for inclusion in the pancreatic cancer treatment regimens. This talk presented some of our efforts in the design, development and clinical translation of HSP inhibitors and in the rational selection of pancreatic patients who are more likely to draw a benefit from such drugs.

WWW.PANCREATIC.ORG

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APA/HIRSHBERG SYMPOSIUM: CELEBRATING 10 YEARS OF THE HIRSHBERG SEED GRANT

Novel Therapeutic Targets (EphB4, Axk, GRP78) in Pancreatic Cancer PARKASH GILL, MD USC NORRIS CANCER CENTER

Locally advanced or metastatic pancreatic carcinoma is primarily treated with cytotoxic chemotherapy. Most recent entry to these agents includes Abraxane and Erbitux. Understanding the genetic basis and pathways activated in pancreatic carcinoma provides opportunities to develop novel therapeutics. We are investigating two novel targets which include receptor kinases EphB4 and GRP78. EphB4 receptor kinase is aberrantly expressed in tumor cells and its ligand EphrinB2 is expressed in the tumor endothelial cells. EphB4-EphrinB2 interaction leads to bidirectional signaling promoting tumor cell survival and progression. We are investigating the induction of EphB4 in pancreatic ductal adenocarcinoma (PDAC) in spontaneous tumor model in which mutant KRAS is induced and p53 is deleted. Preliminary data supports the hypothesis. Secondly, we are investigating if the deletion of EphB4 in the same cells will reduce the development of PDAC. Once proven, we will investigate the efficacy of blocking EphB4-EphrinB2 interaction and signaling using decoy soluble EphB4 receptor extracellular domain (sEphB4) fusion protein containing full length human seru Albumin

(sEphB4HSA). Albumin fusion promotes drug delivery into the tumor and markedly enhances pharmacokinetics. sEphB4HSA has potent antitumor activity as a single agent and when combined with Gemcitabine in orthotopic models. Studies will become the basis for the conduct of clinical investigation in patients with pancreatic carcinoma. GRP78, a stress response protein is highly induced in pancreatic cancer. GRP78 also translocates from the endoplasmic reticulum to the tumor cell surface where it interacts with several membrane proteins and activate PI3K pathway. Genetic deletion of GRP78 attenuates several genetically defined spontaneous tumors models. We are thus targeting surface GRP78 as a potential therapeutic agent. We have identified a monoclonal antibody that binds surface GRP78 with high affinity, induces endocytosis and degradation and inhibits PI3K signaling. We plan to investigate the surface GRP78 expression in spontaneous PDAC tumor model in which mutant KRAS is induced and p53 is deleted. Next we will investigate the efficacy of GRP78 specific antibody as a single agent and in combination with Gemcitabine and Albutaxol. These data will provide the foundation for go-no-go decision to conduct human clinical trial in pancreatic carcinoma using GRP78 specific humanized antibody.

Targeting Histone Demethylases in Pancreatic Cancer ALEXANDROS TZATSOS, MD, PHD MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER

By employing a systems biology approach we have identified members of the Jumonjidomain containing histone demethylase family as important oncogenes in pancreatic cancer. Gain and loss of function experiments coupled to genome-wide gene expression and chromatin immunoprecipitation studies showed that histone demethylase KDM2B subverts cellular differentiation and sustains metabolic homeostasis in pancreatic cancer. Given the reversibility of epigenetic changes, ongoing efforts to target KDM2B may provide new approaches for the treatment of pancreatic cancer.

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APA/HIRSHBERG SYMPOSIUM: CELEBRATING 10 YEARS OF THE HIRSHBERG SEED GRANT

Advances in Early Detection in Pancreatic Cancer Pancreatic cancer is a complex heterogeneous disease and much effort has been put forth to try to improved outcomes in patients who develop it. This is particularly relevant as a recent report has found that if outcomes are unchanged, pancreatic cancer will become the second leading cause of cancer death in the United States by 2030. Approaches to improve outcomes in pancreatic cancer focus on 3 areas: improved treatment strategies, early detection, and prevention. While the largest research effort has been directed to developing new therapeutics, ultimately

DIANE M. SIMEONE, MD UNIVERSITY OF MICHIGAN

we will gain greater headway if we develop methods to detect pancreatic cancer at its earliest stages. While over 2000 studies have been published on early detection biomarkers for pancreatic cancer, progress has been slow. Most studies are done in late stage rather than early stage samples and lack proper disease controls, including chronic pancreatitis, diabetes, and biliary obstruction. An effective biomarker test for pancreatic cancer will need to have a very high sensitivity and specificity to be useful as a screening tool. Despite these obstacles, collaboration among high volume centers in early stage sample collection, and in biomarker development and validation, partnered with technological advances in measurements in circulating DNA and tumor cells, may lead to acceleration in the pace of finding an early detection strategy for the disease.

Epithelial to mesenchymal transition and stemness in pancreatic cancer MOUAD EDDERKAOUI, PHD CEDARS-SINAI MEDICAL CENTER & UNIVERSITY OF CALIFORNIA, LOS ANGELES

Smoking is a major risk factor for pancreatic cancer. We developed novel mouse models of pancreatic cancer induced by smoking. We used two pancreatic cancer mouse models induced by overexpression of KRAS with two different degrees of disease complexity. In the first model we injected EL-KRAS mice with smoking compound NNK and in the second model we exposed Pdx1-Cre; LSL-Kras mice to cigarette smoke in smoking chambers. We measured the effect of smoking on pancreatic epithelial (PanIN) lesion formation, fibrosis, proliferation, death pathways, epithelial to mesenchymal transition (EMT), and stemness. EMT is a critical step for cancer cells metastasis and leads to the acquisition of cancer stem cells features including resistance to treatments. We found that smoking caused stimulation of PanIN lesion WWW.PANCREATIC.ORG

formation in both models. Smoking significantly stimulated fibrosis, cell proliferation and inhibition of apoptosis, and in a lesser extend stimulated inflammation. Importantly, we found that smoking stimulated EMT even in early PanIN lesions in mice pancreas. The levels of vimentin and transcription factor Zeb1 were increased in the pancreas of mice exposed to smoking. Whereas, E-cadherin level was decreased. Stem cell markers CD133 and sox2 levels were increased by smoking. Inhibition of Zeb1 using specific siRNA prevented EMT and stemness in pancreatic cancer cells MIA-PaCa-2 and AS-PC1. Combination of Zeb1 inhibition and Gemcitabine induced cell death and prevented EMT and acquisition of cancer stem cells features in pancreatic cancer cells. This data indicate that EMT and stemness occur at early stage of pancreatic cancer development and suggest the combination of gemcitabine with EMT inhibitor to prevent metastasis and development of resistance to treatment.

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APA/HIRSHBERG SYMPOSIUM: CELEBRATING 10 YEARS OF THE HIRSHBERG SEED GRANT

Obesity, Inflammation, and Pancreatic Cancer Development KATHLEEN HERTZER, MD, PHD UNIVERSITY OF CALIFORNIA, LOS ANGELES

There is epidemiologic evidence that obesity increases the risk of several human cancers. Various underlying mechanisms, including inflammation and insulin resistance, are proposed. However, the driving mechanisms in pancreatic cancer are poorly understood. The goal of our study was to develop a model of diet-induced obesity and pancreatic cancer development in a state-of-the-art mouse model, which resembles important clinical features of human obesity, e.g. weight gain and metabolic disturbances. Offspring of Pdx1-Cre and LSL-KRASG12D mice were allocated to either a diet high in fats and calories (HFCD; ~4,535 kcal/kg; 40% of calories from fats) or control diet (CD; ~3,725 kcal/kg; 12% of calories from fats) for 3 months. Compared to control

animals, mice fed the HFCD significantly gained more weight and developed hyperinsulinemia, hyperglycemia, hyperleptinemia, and elevated levels of IGF-1. The pancreas of HFCD-fed animals showed robust signs of inflammation with increased numbers of infiltrating inflammatory cells (macrophages and T-cells), elevated levels of cytokines and chemokines, increased stromal fibrosis, and more advanced PanIN lesions. Our results demonstrate that a diet high in fats and calories leads to obesity and metabolic disturbances similar to humans and accelerates early pancreatic neoplasia in the conditional KRASG12D mouse model. This model and findings will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity as well as to evaluate dietary-and chemo-preventive strategies targeting obesityassociated pancreatic cancer development.

SIDMAP Contributions to Cancer Metabolomics One of the key contributions made by Agi Hirshberg to industry and academia was her founding of SiDMAP, a company which is focused on using tracer-based metabolomics technology in drug development research and in the investigation of cancer metabolism. SiDMAP’s analytical approach is designed to investigate metabolic pathways in vitro, in vivo, or in human subjects using a single of 13C labeled tracer such as [1, 2-13C]-glucose or [U13C]-palmitate. The metabolism of these 13C labeled substrates introduces 13C carbons into a multitude of metabolic intermediates that are central to glucose and TCA cycle metabolism. SiDMAP, through the use of proprietary technology, determines in key metabolites the number of 13C incorporated and their relative positions within the molecules (isotopomer distribution), which are reported in the form of a heat-map (SiDMAP Array®) for easy visual interpretation of metabolic fluxes. Thus, the SiDMAP Array®

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VAY LIANG W. GO, MD UNIVERSITY OF CALIFORNIA, LOS ANGELES

depicts the overall system-effect of diseases, drugs, age and individual variations on metabolic pathways. Unlike other metabolomics technologies, SiDMAP technology, with the use of specifically chosen 13C or 2H labeled substrates, provides information on metabolic fluxes of energy/substrate producing pathways. The optimal utilization of chemical energy and production of carbohydrates, amino acids and fatty acids by the cell, defines the homeostasis of the cell which is an important parameter of a biological system only measured by SiDMAP technology. With this cutting edge technology, SiDMAP has provided analytical and consultative services to a wide range of pharmaceutical companies in their development of anticancer, anti-inflammatory or anti-diabetes treatments. It has also aided academia in understanding cancer metabolic phenotypes in tumors carrying specific mutations such as IDH and fumarate hydratase. SiDMAP has been successfully validated in a vast array of human diseases, a non-exclusive list is provided on their website, www.sidmap.com. YOU CAN HOPE OR YOU CAN HELP®

APA/HIRSHBERG SYMPOSIUM: CELEBRATING 10 YEARS OF THE HIRSHBERG SEED GRANT

Salivary Biomarker Development for Pancreatic Cancer Detection DAVID WONG, DMD,DMSC UNIVERSITY OF CALIFORNIA, LOS ANGELES

In recent years, sparked by initiatives from the National Institute of Dental & Craniofacial Research (NIDCR), saliva has attracted widespread interest as a diagnostic medium for rapid, pointof-care testing. The advantages of using saliva for disease diagnostics include ease of access, noninvasive sample collection, increased acceptance by patients, and reduced risks of infectious disease transmission. Lack of detection technology for early stage pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. New strategies and biomarkers for early detection are sorely needed. We conducted a prospective sample collection and retrospective blinded validation to evaluate the performance and translational utilities of salivary extracellular RNA and microbial biomarkers for the non-invasive detection of early stage resectable pancreatic cancer. Two biomarker discovery technologies were used to profile

transcriptome and microflora in saliva. The Affymetrix HG U133 Plus 2.0 Array was used to discover altered gene expression in saliva supernatant. The Human Oral Microbe Identification Microarray (HOMIM) was used to investigate microflora shift in saliva pellet. Biomarkers selected from both studies were subjected to clinical validation using an independent sample set of 30 early stage pancreatic cancer, 30 chronic pancreatitis and 30 healthy controls. Two panels of salivary biomarkers, including twelve mRNA biomarkers and two microbial biomarkers were discovered and validated. The logistic regression model with the combination of four biomarkers (KRAS, MBD3L2, ACRV1 and DPM1) could differentiate pancreatic cancer patients from non-cancer subjects (chronic pancreatitis and healthy control), yielding a ROC-plot AUC value of 0.971 with 90.0% sensitivity and 95.0% specificity. The salivary biomarkers possess discriminatory power for the detection of early stage pancreatic cancer, with high specificity and sensitivity. These reports provided the proof of concept of multiplex salivary biomarkers for the noninvasive detection of a systemic cancer and paved the way for prediction model validation study followed by pivotal clinical validation.

10th ANNUAL AGI HIRSHBERG

SYMPOSIUM ON PANCREATIC CANCER

Saturday, February 8, 2014 UCLA Faculty Center Register at www.Pancreatic.org

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HOST AN EVENT

Inspiring Hope & Engaging Your Community 2013 was an amazing year for the Hirshberg Foundation thanks to those families who organized fun and creative fundraising events in their local communities! Across the country our event hosts passionately shared our message of hope and rallied their communities to help fund the necessary research toward a cure. Events like the popular Cupcakes & Champagne and the exciting Style-A-Thon were great successes. While new ideas emerged there were also unique twists on run/walks and golf tournaments as well. Kudos to everyone who hosted an event in 2013! We invite you to become a champion in the fight against pancreatic cancer by taking the first step and creating an event in your community. Help bring us closer to our goal of finding a cure for pancreatic cancer. Recently the Foster family came together to host their 1st Foster the CURE Golf Tournament in Sioux City, Iowa. Check out the following article including personal event tips they’ve shared about their experience.

Get Started Today! Visit www.Pancreatic.org “How You Can Help”

Have questions about creating an event & fundraising? Contact sbanks@pancreatic.org

Review our online Event Guidelines

IDEAS OF FUNDRAISING EVENTS YOU CAN PLAN IN YOUR COMMUNITY:

HOLIDAYS & SPECIAL OCCASIONS “MISSION VIEJO TURKEY CHASE"

CONCERTS & BENEFITS “COTTONFEST BLUEGRASS FESTIVAL”

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FAMILY TRADITIONS “DALE BURTON ALLIGATOR WALK”

FUNDRAISING AT WORK “CANYON SALON STYLE-A-THON”

SPORTS & HOBBIES “DAL BON GOLF TOURNAMENT”

SCHOOLS, CLUBS, & FRATERNITIES “WAYNESBURG U. WOMEN’S SOCCER MATCH”

YOU CAN HOPE OR YOU CAN HELP®

HOST AN EVENT FOSTER THE CURE'S 1ST GOLF TOURNAMENT

How to tee-off your first event by FOSTER THE CURE*

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ur dad, Jim Foster was diagnosed with pancreatic cancer on September 16, 2011 and lost his battle 4 months later at 56 years old. He was a husband, dad, grandpa, friend, and respected colleague. He was a truly genuine person and always put his family first. He deserved a lot more time than he was ultimately given. We knew the prognosis was grim but fought with him for those four months and when he lost his battle, we knew we couldn’t stop fighting. “FOSTER the Cure” was formed to help raise funds for pancreatic cancer research to hopefully allow someone else to thrive with their life in a way that our dad couldn’t. After the success of our local rummage sale in 2012, we began setting our sights even higher so this year held our first golf tournament! We pulled together as a team and were able to make our first tournament, which included a luncheon and raffle, a success. Everyone associated with FOSTER the Cure believes that one day all of the good that the Hirshberg Foundation is doing will be able to provide a cure for pancreatic cancer. Our dad wasn’t given that chance and when you lose hope, you lose your life. We will continue to fight for our dad and raise money for the Hirshberg Foundation so that others won’t lose hope.

Here are some tips we learned when planning our event: ACCEPT A HELPING HAND… Dad golfed at the Sun Valley

Golf Course and they were very helpful in planning the tournament with us. We divided up the duties of the golf tournament so one person wouldn’t get overwhelmed. SET GOALS… On top of creating awareness we wanted to

GET THE WORD OUT… We did interviews with all the local news

stations and a local radio station interviewed us and ran our PSA up to the day of the event. TRY SOMETHING NEW… We started a facebook page for FOSTER

the Cure and regularly posted updates! CHALLENGE YOURSELVES… We accomplished things we’d never

done before by working with the golf course, planning logistics & rules, registering golfers, requesting raffle prizes, approaching sponsors, and more. OVERCOME OBSTACLES… Before the tournament it began to

rain and didn’t stop. It wasn’t enough to postpone the event and the golfers stuck it out and went through the course like it was sunny and 85 degrees! THANK SUPPORTERS… We thanked sponsors by placing signs at each hole, using social media and writing thank you notes. We offered golfers additional items including a team memorabilia photo at the first hole. The winning team received a trophy. We appreciated the golfers sticking it out with us and next year can only be better!

*FOSTER the Cure consists of Jim Foster’s family – his wife: Karen Foster, his children: Brandi Duerksen, Monica Colella, Kristin Casotti, and Jamie Foster, and his children’s spouses and his grandchildren.

raise as much money as we could. We were able to obtain sponsors including a local hospital, hotel, businesses, and a local family (the Kochs).

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EVENT SPOTLIGHT THE CANYON SALON'S 2 ND ANNUAL STYLE-A-THON

An afternoon fit for a queen raises awareness with style

This summer the owners of The Canyon Salon in Westlake, CA transformed their stylish boutique salon into a spectacular celebration to honor the memory of Sharon Perry. Sharon lost her battle with pancreatic cancer in 2012 only a couple days before the first Style-A-Thon was held. This year her daughter Shannon, son Randy Newhart, and two nieces Christy Calfati & Nikki Corzine hosted the 2nd Annual Style-A-Thon with a deeply changed and equally passionate perspective. The community poured in, from babies on up to a 90 year old. Supporters made appointments for blow-drys, deep conditioning treatments, manicures, braids, haircuts, and much more. Nearly 400 people came through the doors eagerly anticipating appointments with stylists that would go above and beyond. Baskets filled with expensive hair care items were displayed for raffle and the festivities included a photo booth, glitter tattoos and face paint for the kids. A DJ played tunes to energize everyone as they enjoyed an elaborate spread of food and beverages including a purple martini named “The Sharontini.” A special treat was in store for one local woman who was selected as “Queen for the Day”. She is the caregiver for her husband, who is currently battling cancer. Event organizer Ingrid Jensen said “The community was

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really able to get involved, all in the name of someone they knew and loved. She was absolutely touched and delighted to be pampered all day! She had a facial, her makeup done, a manicure, and her hair magnificently styled. It was a pretty powerful event!” The Canyon Salon has become a place where staff and clientele continue to support the family’s efforts to raise awareness of pancreatic cancer. “This event has been so successful two years running now. Not only is it a success in terms of the money raised but also for the growing knowledge our community has of this horrible disease. It is an avenue for loved ones to put thoughts to action”, says Shannon. Canyon Salon staff make the event possible by donating their time and they’ve continued the tradition of raising funds as TEAM SHARON at the LA Cancer Challenge. Shannon declared, “The Style-A-Thon will run every year for years to come. A generous friend of my mother’s paid $1000 for his haircut! Any proceeds raised in honor of my mother, Sharon Perry, will always go to the Hirshberg Foundation. The group behind the cause is such a dynamic, beautiful, warm and dedicated group of people. My mother and I shared wonderful moments with the people of the foundation. That is priceless.”

YOU CAN HOPE OR YOU CAN HELP®

EVENT SPOTLIGHT 3 RD ANNUAL JULIE DURMASKIN MEMORIAL GAME DAY

Playing a part in the fight against pancreatic cancer

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aturday, June 22nd marked the 3rd Annual Game Day hosted by Debbie Bernstein. Debbie organized the event in memory of her sister Julie Durmaskin who passed away in 2010 at age 50. Game enthusiasts came out for a fun filled afternoon playing board games, cards, Scrabble, and even Wheel of Fortune. The past two years Debbie has welcomed friends, family, and the community to help raise awareness, fundraise for pancreatic cancer research, and enjoy some friendly competition. “My sister, Julie, LOVED to play board games-we did it a lot as kids. She was amazing. When she was playing, it was very difficult for anyone else to win! She especially loved word games and introduced me (and half of the state of Nebraska) to Bananagrams, which is still one of my favorite games” shared Debbie. Game Day was held in the shaded picnic area of Barrington Park & Recreation Center where people (and dogs!) of all ages, from 8 to 86 years old, were in attendance. Some of the more serious players played games of Chess, Poker, or Scrabble. If you were looking to break some rules and play for laughs, Wheel of Fortune, Taboo, and Bananagrams were also laid out on the game table for the taking. Everyone enjoyed lunch from Chin Chin and various munchies placed on each picnic table. Local businesses including Whole Foods, Toscana, Ralph's and The Massage Place showed

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their support by donating gift certificates for the raffle. Over 40 people came out for games, lunch, and a fun time with friends. This year Debbie also wanted to show her unwavering support for her dear friend Don Winett who was diagnosed with pancreatic cancer earlier in the year. “He’s a friend and someone I love very much,” said Debbie. He not only attended the fundraiser, but was joined by his aunt, cousin, and friends. In October 2013, at the age of 61, Don lost his battle to pancreatic cancer. Following the event Debbie described Don with a fondness, “Don loved to play [board games] too. He and I would play Trivial Pursuit and he was great at it!” Debbie created a new H.E.L.P. Fund on the Hirshberg website to raise donations and participants made contributions at the event. Funds raised this year surpassed previous years by thousands of dollars! “It was challenging to organize, it took me a couple of months to arrange the gift card and food donors,” said Debbie, but the hard work paid off. The event was a huge success and a great day for everyone. Shortly after the event Debbie was already talking about the 4th annual Julie Durmaskin Memorial Game Day!

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EVENT SPOTLIGHT FISHING FOR A CURE: THE LARRY MEISTER MEMORIAL TROUT & BASS TOURNAMENT

Fighting Cancer with a Fishing Rod

As winter approaches many outdoorsmen and women eagerly anticipate the next Fishing for a Cure Trout and Bass Tournament. Doug Carlson, a pancreatic cancer survivor for over 3 ½ years, hosted the first Fishing for a Cure event last year. Doug, a licensed fishing guide and angler, decided to organize a new unique event to raise awareness. Doug took Lake Casitas by storm with his signature “Fishing for a Cure” boat. Participants at varying skill levels came out to support the cause while trying to catch the largest bass or trout. Ready to compete in the Trout Derby, several families brought their children and boats out to support the fundraiser. “Bass appeared to be on the chew, as they were the predominant species brought to the scales throughout the event,” said Doug. The gazebo at Lake Casitas Recreation Area was filled with goodie bags for participants, scales to weigh the fish, awards for the winners, and folks who came out to show support. The assortment of bags

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contained t-shirts, a variety of fishing gear, and raffle prizes ranging from gift certificates to iRods and professional guided fishing trips. By the end of the afternoon 35 anglers in three age divisions competed for the coveted "Cup" and first place divisional plaques. Ryan Caulfield of Ventura was the last angler to make his way to the stage. Weighmaster Paul Baradat called out "5.24 pounds" and the enthusiastic crowd that had assembled cheered the eventual Cup winner. Mrs. Barbara Meister was on hand to present Caulfield with the "Cup" named after her late husband, Larry Meister, a local outdoorsman who lost his battle with pancreatic cancer almost seven years ago. Barbara, son Michael, daughterin-law Faryl, and daughter Sherry were all in attendance to support Doug and honor the memory of their loved one. The Carlson family remains dedicated to the fight against pancreatic cancer. This event, however, was a personal endeavor by Doug. He’s now raising awareness while sharing something he enjoys. “The common theme this year was having fun, and, of course, fishing for a cure!

YOU CAN HOPE OR YOU CAN HELP®

SPECIAL EVENTS 2014

Benefiting the Hirshberg Foundation for Pancreatic Cancer Research APRIL 27, 2014 2nd Annual Gourmet Cupcakes & Champagne Location: The Federal Bar, North Hollywood, CA Contact: gourmetcupcakes4acure@gmail.com

JUNE 2014 2nd Annual FOSTER the Cure Golf Tournament Location: Sioux City, IA — Contact: info@pancreatic.org H.E.L.P. Fund: www.pancreatic.org/fund/jim_foster

AUGUST 2014 6th Annual Dal Bon Memorial Golf Tournament Location: Auburn, CA Contact: info@pancreatic.org — www.teamdalbon.org

SEPTEMBER 2014 6th Annual Thrill In Da-Ville Labor Day Race Location: Dawsonville, GA Contact: bballjanet@bellsouth.net

OCTOBER 2014 4th Annual Pursuit of Wellness 5K Walk/Run Location: Dorset, VT Web: https://www.facebook.com/thepursuitofwellness

OCTOBER 2014 7th Annual Kevin Miya Golf Classic Location: Brentwood, CA Contact: silvanic@pacbell.net

NOVEMBER 8, 2014 5th Annual Dale H. Burton Alligator Walk Location: Winston-Salem, NC Web: www.alligatorwalk.com

NOVEMBER 2014 Annual Fore-A-Cure 50/50 Raffle Location: High Point, NC Contact: Kimpope29@yahoo.com

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MARCH 9, 2014 Purple People Cheer Station at L.A. Marathon Location: Los Angeles, CA— hirshbergtrainingteam.com Contact: sbanks@pancreatic.org

MAY 18, 2014 2nd Annual Tour de Pier Location: Manhattan Beach Pier, Manhattan Beach, CA Contact: info@pancreatic.org — www.tourdepier.com

JUNE 2014 4th Annual Julie Durmaskin Memorial Game Day Location: Los Angeles, CA — Contact: info@pancreatic.org H.E.L.P. Fund: www.pancreatic.org/fund/durmaskin

AUGUST 2014 3rd Annual Style-A-Thon Location: The Canyon Salon, Thousand Oaks, CA Contact: Ingrid@thecanyonsalon.com

OCTOBER 26, 2014 17th Annual L.A. Cancer Challenge Location: Los Angeles, CA Contact: info@pancreatic.org — www.lacancerchallenge.com

OCTOBER 2014 6th Annual Kick Pancreatic Cancer Soccer Match Location: Waynesburg University - Waynesburg, PA Contact: info@pancreatic.org

NOVEMBER 8, 2014 8th Annual Cottonfest (Bluegrass Concert) Location: Etowah Lodge, Etowah, TN Contact: Bluegrass_4_ever@comcast.net

NOVEMBER 2014 5th Annual Mission Viejo Turkey Chase 5k Location: Mission Viejo, CA Web: www.mvturkeychase.com

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MAKING A DIFFERENCE

Going the Extra Mile for Families Impacted by Pancreatic Cancer by MATT DIMMER

Editor’s Note: Matt Dimmer is the founder and CEO of The Extra Mile, a nonprofit which collects donations of air miles and gives them to people who wouldn't have otherwise had the means to visit loved ones diagnosed with pancreatic cancer. The Hirshberg Foundation refers families in need to his organization. Here is his story.

P

ete Dimmer was an amazing man. He was my father. My coach. A tinkerer. A fisherman. A hunter. A kind soul. He was known as the go-to guy for stuff to do around the house and in the community. Until November of 2011, my dad was a pretty healthy 65 year old. He began having some serious stomach pains, so he went to get it checked out. Initial diagnosis was a gall bladder issue, so he scheduled surgery. While scoping him, they determined the gall bladder was actually fine; it was his pancreas causing the problems. After this was missed in an initial CT scan, he ended up with an inflamed pancreas later diagnosed as pancreatic cancer - Stage 4. My wife Jess and I had just relocated to LA from Chicago, where my dad lived. We were settling into new jobs and new lives, making new friends. But without thinking twice, we decided to travel home every chance we could get. Every weekend. Sometimes longer. Because we didn’t want to miss a moment. And… because we could. Because every holiday, weekend, day, minute, second… could be our last together. It wasn't long after a holiday visit before we had 'the talk.' That conversation I never imagined having with my dying father. The one that makes me tear up watching it in movies. The one where he told me there's nothing that could make him better and he only had a couple weeks left to live. I tried desperately to hold back the wave of emotions that came over me. I fought to be the strong one, but eventually gave in and just hugged him sobbing. We got through it, I told him how much I'd miss him, how great it was to have him as a coach, a dad, and all the other memories I'll cherish forever. About a month before dad passed away, it struck me. What do people do when they can’t be there? Jess and I had been so

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fortunate, to be able to make all those trips without so much as blinking. It pained me to think of those who couldn’t see their loved ones before their passing or be able to talk about life prior to passing… simply because they couldn’t afford the cost of travel. Looking back on it now, though it is all still so painful to recall, I feel so blessed that I was there. I was there right after he was diagnosed. I was there when he got sicker. I was there for his last cognizant moments. I was there for his last moments of life. And I was there when he died. I was inspired to create a non-profit company. Our mission is to give those who cannot afford to travel the opportunity to visit their loved ones dying of cancer, so they can cherish the last holiday, weekend, day, minute, second… together. I was, and still am, determined to make the Extra Mile a success in his honor and was happy that I could show him some of our progress on one of my last trips home. In my father’s last days and beyond, stories came pouring back to us. How he — as a father, coach, friend, neighbor — always went the extra mile to help anyone in need. So our name, The Extra Mile, is my way of honoring my father and carrying on his legacy. Now others can have the chance I had: to say goodbye. To learn more about The Extra Mile, visit www.thextramile. org. To donate miles, visit www.mileage.org/thextramile. YOU CAN HOPE OR YOU CAN HELP®

MAKING A DIFFERENCE

Pants Off Racing, Inc. — Adopt-A-Family Program by D.R. AMATO

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y mom was diagnosed with pancreatic cancer in 2006. In 2009 she travelled to Los Angeles from Ohio to participant in the LA Cancer Challenge with 30 team members from across the country in tow. Team Nancy Pants was named after our mother Nancy “Pants” Amato, because we all know who wears the pants in the Amato family! No one could have imagined the impact that day had on my family.

for endurance sports, (ie. triathlons, marathons, 10k’s, 5k’s, etc) and our love for our mother, we have formed a powerful group of supporters who are passionate about making a difference in someone else’s life. Our greatest efforts revolve around the holiday season when POR – or the Meerkats as we like to be called - “adopts” local families that are dealing with the same hardships that we once experienced as a family.

Soon after my mother’s diagnosis in 2006 we all realized that this hardship was not just about us –there were a whole lot of people out there who cared about our family. It took some time, but we finally got to the point where we looked outside of ourselves and saw that there were many other families just like us, facing the exact same things we dealt with. We were lucky that those around us and, unexpectedly, the local support from the community, were there for us no matter what. And, truly, that is what made the biggest impact on us as a family and our moms’ fight with this disease.

We worked with the Hirshberg Foundation to get in touch with pancreatic cancer families that might be in need of holiday help. Knowing that it can be extremely difficult for patients to get into the holidays spirit, we decided we wanted to help. From trimming the tree to providing gifts, delivering holiday dinners to lending a friendly “ear” for someone to talk to, POR is there so that families can just focus on spending time with each other. This past year, we "adopted" three local families coping with a recent pancreatic cancer diagnosis. We obtained a gift list from the families and distributed the lists to our POR Meerkats near and far. The amount of gifts contributed by those across the country was overwhelming.

Eventually my brother Pat and I created the non-profit Pants Off Racing, Inc, “POR” as a way to show our appreciation and give back all the love and support we have received as a family since our mothers’ diagnosis. Combining our love

Each holiday season we are reminded of the impact we are able to make in the local community by the families that we have adopted. The relationships formed through this program extend beyond the holiday season and it has been our goal to not only help and assist these families during the most difficult of times, but to also be there for them when the initial shock and reality of this disease begins to dwindle. The POR Adopt-A-Family program only scratches the surface of the impact we make on the lives of others to make a lasting connection with the pancreatic cancer community. The Hirshberg Foundation motto, “You Can Hope or You Can HELP,” is something we take to heart. It is our goal to live and act within our means to help as many patients and families dealing with the same hardships we dealt with. That is the reason we created the POR Adopt-a-Family program – to assist families in need and know that we can make a difference.

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LA CANCER CHALLENGE

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s the sun arose amidst an unusually dense foggy morning of Sunday October 27, more than 3000 runners, walkers and groups of volunteers gathered at the Veteran's Administration Grounds in West LA to show their support in the fight against pancreatic cancer. This year’s 16th Annual LA Cancer Challenge marked another successful event, bringing the total raised in the event’s history to 5 million dollars. We are thankful to our loyal sponsors, including Wells Fargo who returned as our Presenting Sponsor. Our team captains are also a loyal bunch, having collectively raised more than $400,000. Congratulations to the awesome Marvin’s Marvels, the team that was both the largest and the highest fundraising team. In addition to the 5K, the 10K and the Kids Can Cure Fun Run, we added a new event to our line-up. Called “Both 5K & 10K”, runners who registered to run both races had their times combined and winners were announced for both the top male and top female. Preparations have already begun for the 17th Annual LA Cancer Challenge, to be held on Sunday, October 26, 2014. Thank you to all the team captains, runners, walkers, volunteers, sponsors and exhibitors for fighting with us. We will not stop until we find a cure! To register or get more information, please visit www.LACancerChallenge.com.

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YOU CAN HOPE OR YOU CAN HELP®

LA CANCER CHALLENGE

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LA CANCER CHALLENGE

Team Highlight: The Dedolians ALISHA BRENDIS, TEAM CAPTAIN

commitment to pancreatic cancer research from the beginning. Although we’ve supported the LA Cancer Challenge in one way or another for many years, we’ve decided to step up our efforts this time around. We promoted the event not only with our staff, but with our friends, partners and vendors. Our enthusiasm caught fire and at 13 strong we fielded our biggest team to date and merrily dubbed them “The Dedolians”. The team has even engaged in a friendly fundraising competition which helped to drive our contribution numbers higher. Go team!

Dedola Global Logistics began working with Ron and Agi Hirshberg 20 years ago when they owned and operated their company, Agron. We continued our relationship with the Hirshbergs when Agi and Ron’s son Jon started their next venture, JR286, and currently provide logistics and compliance services to ENIJR286. As such, we have been involved with The Hirshberg Foundation and their

This year has definitely been a family affair for us. Our team consisted of customers, vendors and several family members. Our youngest teammate, Annemarie, was just 18 months old. One member of our team, Lisa, has been touched personally, having lost her father to pancreatic cancer a few years ago. Lisa also joined us for the inaugural Tour de Pier event last May. We are proud to have her as one of our Dedolians and look forward to supporting the Hirshberg Foundation in the future.

Team Highlight: Chuyera MONICA MORENO, TEAM CAPTAIN

May 05, 2011 my aunt "Chuyera" was diagnosed with pancreatic cancer. It was from that day on that our whole lives would change for ever. My aunt was one of the most beautiful and most charismatic women I knew. She was always laughing and was always very welcoming, kind, and loving. She never once complained about her illness and stayed strong through it all. On August 30, 2011 we lost my aunt 'Chuyera' to pancreatic cancer. It was then when my family and I learned about the LA Cancer Challenge. October 2011 was the first year my family and I participated in the LACC. It was the most gratifying experience for all of us when we crossed that finish line - knowing that we had done it for our Aunt and so many fighters out there

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struggling every day with this horrible illness that claims thousands of lives each year. Pancreatic cancer is not a cancer that many people are aware of, it is usually not detected until it is too late. Running for a cure is the best feeling there is, knowing that you are making a difference in someone's life to raise funds for research and to find early detection methods. We are excited to have run in our 3rd LACC this year and look forward to next year. YOU CAN HOPE OR YOU CAN HELP®

LA CANCER CHALLENGE

Team Highlight: Martin's Marchers CHRISTEL SCHOENFELDER, TEAM CAPTAIN

Our family became entangled in the fight against pancreatic cancer last June when Regina Martin received "the diagnosis." Based on our research, we learned pancreatic cancer is essentially a death sentence. Although Regina had been energetic, vibrant & young at heart, we watched her become fatigued, have trouble breathing, and lose weight.

A few short months later, we were wearing purple at her funeral and the reception hall was a sea of purple. But our story does not end there. A family member ran across the Hirshberg Foundation website. Our family organized a team (Martin's Marchers) & participated in our first L.A. Cancer Challenge 5K walk. We created t-shirts, wore carnival masks, submitted photos for the Tribute Video, wore Tribute Bibs, and designed a square for the Memory Quilt. Our team representatives attended the Team Captain Kick-Off Party which was a great opportunity to meet the wonderful, caring staff of the Hirshberg Foundation. Regina Martin was taken too soon- as are many others with pancreatic cancer. Our team thanks the Hirshberg Foundation for everything they do in their fight against pancreatic cancer and for giving us the opportunity to honor the memory of our beloved Regina Martin!

Team Highlight: Team Guayas MELISSA MACHUCA, TEAM CAPTAIN

I am the granddaughter of Holanda Soriano, who is the inspiration and driving force behind Team Guaya. In the spring of 2007, Holanda was diagnosed with pancreatic cancer. She was the gentle, soft spoken, loving and spiritual matriarch of our growing family: which at the time consisted of her 9 children, 32 grandchildren, 15 great-grandchildren, 2 great-great grandchildren and an ever-loving spouse of 66 years. She fought a tough battle and succumbed to this horrible decease in the fall of 2007. She was 88 years young. She was the first loss to our close-knit family who is still grieving her departure. Undoubtedly, she was the leader of our pack. Shortly after her passing, a co-worker told me about the Hirshberg Foundation, their LA Cancer Challenge walk/run and dedication to pancreatic cancer research and awareness. I immediately felt drawn to the Hirshberg Foundationâ&#x20AC;&#x2122;s mission and knew this was our avenue to honor my grandmother and take part in the fight against pancreatic cancer. We have participated in the LA Cancer Challenge since 2007, initially participating as individuals and later as Team Guayas. WWW.PANCREATIC.ORG

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LA CANCER CHALLENGE

Team Highlight: TAZ (Team Adam Zauder) JULIE CLARKE, TEAM CAPTAIN

When I first attempted to write down my thoughts about Adam’s illness, my experiences with pancreatic cancer and my relationship with the Hirshberg Foundation, it was extremely difficult because, the one person that I would have shown this too – to correct all of my mistakes, run on sentences, poor grammar and bad punctuation – Adam - is no longer here. But, let me try… The Hirshberg Foundation first came on to my radar screen very late into Adam’s diagnosis. I was looking for some

After a long, courageous and exhausting battle with pancreatic cancer, Adam Zauder passed away on December 23, 2009. He was only 51. Adam was one of those rare and special individuals who walk into your life and change it forever. I was fortunate enough to have eighteen years with him.

entity that could help me with new ideas or treatments for Adam’s ailment as we were running out of options and time. Unfortunately, by then, it was too late for him. But, the Foundation also gave me comfort, a new purpose, and an added bonus - a way to channel my passion for running. In October 2009, I ran my first LA Cancer Challenge run in support of Adam, and then I signed up to run the 2010 LA Marathon on the Hirshberg Team. This run was meant to be a support run, but training turned bittersweet, and I instead continued on next page

SUNDAY, MAY 18, 2014 MANHATTAN BEACH PIER

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LA CANCER CHALLENGE Team TAZ continued ran this marathon in Adam’s memory. Since then, Team Adam Zauder has run every LA Cancer Challenge – 2010, 2011, 2012, and 2013 - and has consisted of people running locally or virtually in places such as South Carolina, Colorado, and the British Virgin Islands. From the beginning of this journey, my team and I have raised close to $10,000 for pancreatic cancer research. It is our hope that we are doing some part (even if small) in the fight against this devastating disease.

In fact, he never gave up hope during the two year battle he fought against pancreatic cancer. Flying back and forth between LA and New York for treatment, he never complained about how hard it was, or how tired and sick the chemo and radiation made him. So, in his spirit, I too will never give up hope that this disease can be beat. I know the Hirshberg Foundation shares this sentiment and will continue to be relentless in their battle against pancreatic cancer. My teammates and I will continue to support them any way we can.

Adam never gave up – on people, ideas, life and himself.

Team Highlight: Team LANA CHRISTINA SANTORO, TEAM CAPTAIN

On August 18, 2010 at 7:34 am, our Mother Lana took her last breath after a short two-month battle with pancreatic cancer. She passed peacefully in her own home surrounded by her family and a mountain of love. It was the most profound experience of all of our lives and we all felt incredibly blessed to be a part of her passing, as we were her life. Her diagnosis was completely unexpected and as indescribably difficult as those two months were, we were so moved by the enormous outreach of love and support we all received from family, friends and even strangers. Our mother received countless cards, letters, emails and phone calls during that time from people whose lives she had touched and she was incredibly moved by each of them. We learned during this time that not only does it take a village to live and thrive; it takes a village of love and support to transition. Upon her passing, we knew that we wanted to find a special way to keep her memory alive and at the same time support cancer research and the countless others riddled with the horrible disease. We were very happy to cross paths with the Hirshberg Foundation and we immediately signed up for the 2010 L.A. Cancer Challenge. The love and support we had felt during this dark, difficult time continued with an outpouring of support for this beautiful walk and it has now become an annual tradition that we all look forward to participating in. This Foundation and walk have been instrumental in helping our family grieve and give back the love we received during this difficult time. We know that it is LOVE that got us through and it is love that will bring a cure to this epidemic. We thank the Hirshberg Foundation for all of their beautiful work and we feel blessed to be a part of something so important. Today, we are 60 members strong and when we walk, we honor our mother and her beautiful memory, her funny spirit and her love for all people. WWW.PANCREATIC.ORG

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LA CANCER CHALLENGE

Team Highlight: Ohana Means Family JAYME HEYL, TEAM CAPTAIN

Participating in the LA Cancer Challenge has quickly become an annual tradition for our family. Ohana Means Family was formed in the fall of 2012 just before the passing of my grandmother, Kay Shimizu. She was active in the community throughout her life and was probably the most selfless person I know. She volunteered at the Senior Nutrition Program at the Venice Japanese Community Center for over 25 years. She also participated in ikebana (flower arrangement), craft class, and much more. Most of all she will always be remembered for her cooking. Whether it was a full spread of Japanese cuisine on New Year’s Day or a quesadilla after school, grandma showed her love through her cooking. When our team started out we weren’t sure how many people would join or donate. But we were pleasantly surprised when we recruited 25 team members and raised over $4600 in our first year. This year we had 27 members and raised over $5800. We walk/run to remember our loved one, to

show support for people who are currently struggling with this disease, and to raise pancreatic cancer awareness in our community. Most importantly the LA Cancer Challenge is a time each year that our family can get together, reconnect and remind ourselves the true meaning of ohana. Now we can also call the Hirshberg Foundation part of our ohana. I cannot say how appreciative we are of all of the encouragement we get from the staff and volunteers on the day of the event as well as throughout the year.

Team Highlight: The Sandford Family BETTY SANDFORD, TEAM CAPTAIN

The Sandford Family - four generations of women (3 to 86 years) plus one man - were joined by assorted husbands, significant others and family friends to run and walk the LA Cancer Challenge in memory of my husband Jules. All of us loved the experience! We met our goal of 20 team members and more than doubled our financial goal to raise $5000 for developing a cure for pancreatic cure. Our wonderfully supportive friends and relatives and Jules’ partners, staff and clients demonstrated their memory of Jules, their support of the Sandford Family and their concern for ending pancreatic cancer. As the matriarch and Team Captain for the Sandford Family Team, I am grateful to all who participated and to the Hirshberg Foundation for providing the opportunity and for furthering the cause we all share.

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I'd also like to share with the readers of this newsletter a few quotes I’ve received from our supporters. "We need to put a stop to all cancer but pancreatic is the worst"; "You are making a great contribution. Jules would be proud"; “This is fantastic!";"I'm excited to be a part of it"; “While we can't bring Jules back, one of the pleasures of my life was to know him"; "We are cheering for the Sandfords’ from China." Thank you to everyone who supported our team.

YOU CAN HOPE OR YOU CAN HELP®

LA CANCER CHALLENGE

Team Highlight: Milstein Adelman ANTHERINE PERKINS, TEAM CAPTAIN

The law offices of Milstein Adelman began working with The Hirshberg Foundation to raise money and awareness for pancreatic cancer due to our common goals. Milstein Adelman pursues litigation against pharmaceutical products that increase the risk of pancreatic cancer. When informed of The Hirshberg Foundation’s LA Cancer Challenge, the office leapt at the chance to be involved, with 42 employees signing up to run or walk to support survivors and patients with pancreatic cancer. Our team had personal, as well as professional connections to the cause. One of our legal assistants lost his father in 2007 and our team coordinator lost her aunt to pancreatic cancer. These experiences, as well as our drive to protect and support our clients, brought Milstein Adelman together to join the L.A. Cancer Challenge this year. Many of our participants were able to recruit donors and even family outside of the office to participate, creating a diverse team of attorneys, assistants, family and friends. Milstein Adelman is grateful to have had the opportunity to participate in this year’s challenge to help contribute to the fight against pancreatic cancer!

Team Highlight: Mia's Angels D. TOPILTZIN SANCEZ, TEAM CAPTAIN

When asked to write this brief explanation as to why I participate in the LA Cancer Challenge I was dumbfounded. Didn’t know what to do or say; except yes, sure I’ll do it. Then memories of my mother, Maria E. Sanchez, flooded my mind and tears instantaneously flooded my eyes falling down my face. My mother fought this battle from 20042010, beating pancreatic cancer with the help of Dr. Isacoff. She lived for her family and was ecstatic to have beaten this disease. She would later develop leukemia and succumbed to it on March 8, 2013. I participate in this great event for people like my mother, so that they can have the resources available to them that will ensure a better treatment to a disease that is unforgiving.

WWW.PANCREATIC.ORG

I participate in the LA Cancer Challenge because I have to give back to an organization that continues to help families and their loved ones deal with this disease. I do my small part to honor my mother by forming a team every year.

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LA CANCER CHALLENGE

Participant Highlight: Maggie's First 5K by MATT SKINNER

The LA Cancer Challenge has been a part of my family's lives for the last 11 years. When our friend Mark was diagnosed in 2002 we raced in support. Since he succumbed to the disease, we've raced to remember. The race had become a proud yearly tradition. Slowly, we've become more involved and have gotten to know so many people in the Hirshberg organization. The 2013 event will forever hold a special place in my heart. The day after the 2012 LA Cancer Challenge my daughter Maggie decided to get into the race that she had watched from the sideline for the first 7 years of her life. I'm a runner – it is one thing I can say I'm good at doing. Now I was going to get a chance to run with my daughter, what could be better? Obviously when thinking about an 8-year old, "running" is a little strong of a word. I expected her first 5k to involve running, walking and skipping. Before our first training session, I sat Maggie down and talked about her goals (and mine). My rules were simple: 1) If anything hurts, stop! 2) Always have fun and 3) Go at your own pace. That day we ran around the block ONCE. Over the next ten months, the mileage grew slightly (our longest run was 2.65 miles). We experimented with a few different motivational

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systems. We tried jelly beans, PEZ, mints... The memories from our training sessions are countless. The good, the bad and the ugly all blended together. On race day I had no idea what would happen. Maggie never realized she would be running with thousands of other people, so she was a little intimidated. While I pushed her brother in the jog stroller on one side and she grabbed onto her mom’s hand on the other, we started up the "big hill" from the starting line. Maggie kept it simple.....left, right, left, right.....inhale, exhale.....repeat. Mile 1 (still running): "you okay??""Shhhh, Dad!" Mile 2 (Still Running): "want some water?" "It's too cold out for water!" Mile 3 (STILL RUNNING!!): "I can see the finish!" "Me too, looks likes I'm gonna beat you" We ended with an official time 34:51. Good enough for 3rd Place in the 0-9 girls division!!! Four days later the medal has finally come off. However, the memory will last forever and October 26th, 2014 can't come soon enough.

YOU CAN HOPE OR YOU CAN HELP®

PANCREATIC CANCER AWARENESS

30 Days to Shine a Light on a Year Round Battle by SARAH BANKS HIRSHBERG FOUNDATION DEVELOPMENT COORDINATOR

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365

n November 2006 my mother received news that she had pancreatic cancer, she was only 56 years old. Most families were eagerly anticipating a Thanksgiving afternoon of food, family, and football. Meanwhile I was on a flight to LAX and my mom was being wheeled into an O.R. for her Whipple. That November marked the beginning of many obstacles and triumphs to come. Years later November represents the beginning of my mom’s battle with pancreatic cancer and more importantly the anniversaries of her survivorship. Nationally, November is Pancreatic Cancer Awareness Month. It is an invaluable time to bring attention to a disease that is still underfunded, nearly undetectable, and often misunderstood. One month is not enough time to garner all the support and funds we need but we can certainly take this opportunity to bring this disease to the forefront. So, how does raising awareness translate into real tangible results in November or year round? Shine a light on pancreatic cancer and build support. Sharing your story is the one of the first steps to ensuring this disease does not go unnoticed. Like many people, I didn’t know what a pancreas was let alone how swift and deadly this disease is until it affected me personally. The knowledge, support, and the experiences of others was a guiding force. The closer I became with my peers the clearer it was that sharing our stories empowered us. Our voices and actions unite us in this fight and if we want to make progress we cannot remain silent.

WWW.PANCREATIC.ORG

Purple can inspire action! We’ve all come to see that one color can grab the attention of the masses and in turn raise money for research. Before my mom’s diagnosis I knew of only one color that could unite people in the fight against cancer and it was pink. As the pancreatic cancer community makes progress I look forward to seeing more purple! I want to walk into a grocery story in November and see the shelves lined with purple products or watch a sports team wear purple on game day. I want the pleasant surprise of seeing both strangers and friends wearing purple wristbands and ribbons any and every day of the year. Champion your cause by taking action… The goal of the Hirshberg Foundation is to work around the clock to advance research and provide resources & support for patients and families. Individual participation is crucial and you play an important role in the fight against this disease. Start by honoring a loved one and creating H.E.L.P. fund. Utilize our website to host a fundraising event or join us at one of our signature fundraisers. We have the drive and passion to build momentum in this battle. Raising awareness is just the beginning to making great strides in research, increasing survivorship, and ultimately finding a cure! November is National Pancreatic Cancer Awareness Month but we believe 30 days is not enough. This year we created the campaign PC365: A Month is Not Enough to create awareness all year long.

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HIRSHBERG FOUNDATION FOR PANCREATIC CANCER RESEARCH

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