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UCSF Helen Diller Family Comprehensive Cancer Center

Impact Report 2017-2018


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It is difficult for me to convey how transformative the last decade has been for cancer research, or to describe the major role UCSF has taken in our journey to find cures. Alan Ashworth, PhD, FRS President, UCSF Helen Diller Family Comprehensive Cancer Center Senior Vice President for Cancer Services, UCSF Health

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Table of Contents State of The Center Message From President Alan Ashworth

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Celebrating 10 Years of the UCSF Helen Diller Family Comprehensive

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Cancer Center Precision Cancer Medicine Building: Unifying and Expanding Clinical Care

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Integrating Research and Clinical Care: Campus-Wide Collaboration for Greater Impact

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UC Cancer Consortium

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Rising Stars: New Faculty Members Lead to New Discoveries at UCSF

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Initiative Updates Impact Grant Awards: Bold New Approaches to Cancer Research

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San Francisco Cancer Initiative: Uniting to Reduce Cancer

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Global Cancer Program: Looking Far and Wide to Advance Treatment

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Cancer Immunotherapy Program: Unleashing the Body’s Natural Defense Systems

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Center for BRCA Research

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Target Validation Initiative: The Key to Moving Novel Treatments Forward

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Thank You: Give Breast Cancer The Boot

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Message From President Alan Ashworth Dear Friends: It is difficult for me to convey how transformative the last decade has been for cancer research, or to describe the major role UCSF has taken in our journey to find cures. UCSF has the distinction of having the longest-running National Cancer Institute (NCI) comprehensive cancer center in the Bay Area. Also, this year marks the 10th anniversary of our cancer center being named the UCSF Helen Diller Family Comprehensive Cancer Center (HDFCCC). I believe our success is due to the incredible commitment of our faculty, staff, grateful patients, and philanthropists, all of whom have banded together to make the difference when it comes to researching, treating, and curing cancer. This year also marked the launch of UCSF: The Campaign in October. Now is a momentous time for UCSF as we take on grand challenges in health science. As you will read in this report, our cancer programs are central to this major initiative. Our physician-scientists are accelerating their efforts for all of the campaign’s concentrations: decoding life to improve health; leveraging discovery to revolutionize care; and partnering to achieve health equity.

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This year, an independent review by Elsevier, a global publisher of scientific and medical journals, showed that our cancer research is among the world’s most impactful. From patent filings for new cancer therapies to publications on the latest advances in understanding, diagnosing, and treating cancer, UCSF’s HDFCCC is No. 1 in the Western US and among the world’s top five institutions producing the most influential and utilized research. We are also proud of our ranking as the No. 1 cancer center in California, according to this year’s Best Hospitals survey from U.S. News & World Report. The HDFCCC continues to foster and cultivate transformational research programs like our Impact Grants, the expansion of immunotherapy research into patient care, efforts in global cancer health and women’s cancers, the launch of the San Francisco Cancer Initiative, and the construction of the Precision Cancer Medicine Building, which will unify and deliver research advances directly to patients. I am also honored to be the inaugural chair of the UC Cancer Consortium, a partnership with the four other UC cancer centers. I can’t thank you enough for your interest in learning more about the priorities of the HDFCCC. We are immensely proud of our joint accomplishments and look forward to tackling future challenges together. Warmest regards,

Alan Ashworth, PhD, FRS President, UCSF Helen Diller Family Comprehensive Cancer Center Senior Vice President for Cancer Services, UCSF Health Professor of Medicine, Division of Hematology and Oncology, Department of Medicine, UCSF E. Dixon Heise Distinguished Professor in Oncology, UCSF

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Celebrating 10 Years Over the past decade, we have extended our legacy of cancer care, discovery, and innovation, propelling ourselves to new heights with the support of generous donors, volunteers, and grateful patients. We pride ourselves on tackling cancer through collaboration in both research and clinical care. Our faculty investigators in laboratory-, clinical-, and population-based research have advanced our understanding of cancer for the benefit of patients worldwide. Our cancer enterprise has grown exponentially in scope and focus and has allowed us to better treat individuals and families impacted by this disease.

By the Numbers: How Far We’ve Come •

No. 1 recipient of National Cancer Institute (NCI) research funding in California and the longest-running NCI Comprehensive Cancer Center in the Bay Area

No. 1 for cancer care in California and No. 10 nationally (U.S. News & World Report, 2017)

No. 1 in the Western US for cancer research and No. 5 in the world (Elsevier, 2017)

850 ongoing research projects, with budgets totaling $160 million

1,700 patients participating in interventional clinical trials, with 350 adult and pediatric clinical trials ongoing across all cancer types

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3,200 inpatient stays at UCSF Bakar Cancer Hospital in 2016-2017

63,000 adult infusion visits in 2016-2017, with a tripling of infusion bays since 2007

150,000 office and outpatient visits in 2016-2017, a 100 percent increase since 2007


From left: J. Michael Bishop, MD; Peter Carroll, MD, MPH; Mitchel Berger, MD; Dan and Jackie Safier and their children; and Frank McCormick, PhD, FRS, DSc (Hon), commemorate the 2007 opening of the UCSF Helen Diller Family Comprehensive Cancer Center.

Accomplishments Advanced by the HDFCCC •

Continued to build on the excellence of UCSF’s 1989 Nobel Prize-winning discovery of cancer-causing oncogenes by J. Michael Bishop, MD, and Harold Varmus, MD

Dr. Ashworth received the 2017 Brinker Award for Scientific Distinction in Basic Science from Susan G. Komen for his research in exploiting genetic deficiencies in cancer to develop new therapeutic approaches to the disease

UCSF biochemist Peter Walter, PhD, received the 2018 Breakthrough Prize in Life Sciences for his research on the unfolded protein response, which normally protects cells but can cause disease if not functioning properly

Led or participated in Stand Up to Cancer Dream Teams for prostate, breast, pancreatic, and lung cancer, as selected by the American Association for Cancer Research

Supported the Blue Ribbon Panel convened by former Vice President Joe Biden as part of the National Cancer Moonshot Initiative

Led the ATHENA Breast Health Network, a groundbreaking project to improve survival and reduce suffering from breast cancer

Collaborated with five other cancer centers (including more than 40 labs and 300+ researchers) in the Parker Institute for Cancer Immunotherapy to accelerate development of cancer therapies

Led creation of the San Francisco Cancer Initiative (SF CAN) with the City of San Francisco, the first effort for a major city using population science to reduce debilitating effects and deaths from cancer

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The PCMB will play a crucial role in guaranteeing patients timely access to treatment and will help ease the emotional burden of dealing with a challenging disease. Alan Ashworth, PhD, FRS President, UCSF Helen Diller Family Comprehensive Cancer Center Senior Vice President for Cancer Services, UCSF Health

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The Precision Cancer Medicine Building: Unifying and Expanding Clinical Care Designed to house state-of-the-art cancer treatment, the Precision Cancer Medicine Building (PCMB) will open in early 2019, just steps from the UCSF Helen Diller Family Cancer Research Building and UCSF Bakar Cancer Hospital.

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From left: Alan Ashworth, PhD, FRS, president, UCSF Helen Diller Family Comprehensive Cancer Center; Talmadge E. King, Jr., MD, dean, UCSF School of Medicine; Michael and Carol Dollinger; and UCSF chancellor Sam Hawgood at the April 2017 PCMB groundbreaking on the UCSF Mission Bay campus.

Conceptual renderings of the PCMB Infusion Suite (above) and the PCMB Pavilion Lobby (left).

The PCMB will facilitate greater collaboration among researchers, teaching faculty, clinicians, patients, and other providers and will house outpatient cancer care and clinical research. Most important, patients will find it much easier to receive all of their care in one place, in one visit. The PCMB’s six stories and 180,000 square feet will contain 120 rooms for exams, procedures, and consultations; 19 imaging systems; 45 infusion bays; and expanded radiation oncology services. The building features the latest technology, from advanced computational tools to robotics, with room to grow built into the design. These services and supportive care offerings will help us provide even more outstanding and holistic care for patients. The PCMB will play a crucial role in guaranteeing patients timely access to treatment and will ease the emotional burden of dealing with a challenging disease. Social workers, genetic counselors, nutritionists, and symptom management providers will work together in the clinical space to provide patients and families with the support they need.

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It’s a great way for us to share in the combined expertise of UCSF’s various clinical, research, and translational departments and divisions. Alan Ashworth, PhD, FRS

President, UCSF Helen Diller Family Comprehensive Cancer Center

Senior Vice President for Cancer Services, UCSF Health

Integrating Research and Clinical Care: Campus-Wide Collaboration for Greater Impact The HDFCCC Clinical Governance Board – chaired by Dr. Ashworth and comprising UCSF clinical department chairs, the dean of the School of Medicine, UCSF Health leadership, and the HDFCCC deputy director and associate directors – meets monthly and affords members the opportunity to offer input on the entire cancer enterprise and review strategic priorities. This is also a forum in which Dr. Ashworth can bring issues of concern or interest to the Internal Advisory Board and receive input, direction, and resources. “It’s a great way for us to share in the combined expertise of UCSF’s various clinical, research, and translational departments and divisions,” Ashworth says. “We are in a new era of discovery that demands a higher level of communication across disciplines. Successful collaboration is not only the key to discovery but also the key to the best outcomes for our patients, now and in the future.”

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From left: Michael Teitell, MD, PhD, director, UCLA Jonsson Comprehensive Cancer Center; Scott Lippman, MD, director, UC San Diego Moores Cancer Center; Marian Waterman, PhD, deputy director, UC Irvine Chao Family Comprehensive Cancer Center; Alan Ashworth, PhD, FRS, president, UCSF Helen Diller Family Comprehensive Cancer Center; Sam Hawgood, MBBS, UCSF chancellor; Janet Napolitano, president, University of California; John Stobo, MD, executive vice president, UC Health; and John McPherson, PhD, deputy director, UC Davis Comprehensive Cancer Center, at the September 2017 press conference announcing the UC Cancer Consortium.

UC Cancer Consortium The American Cancer Society projects that cancer will kill nearly 60,000 Californians this year alone. To combat the disease, the UCSF Helen Diller Family Comprehensive Cancer Center is among five University of California sites participating in a new collaborative effort that aims to increase access to clinical trials, share research data, and hone cancer prevention efforts across the state. Chaired by Dr. Ashworth, the UC Cancer Consortium will formalize and deepen connections between the UC National Cancer Institute-designated centers, which together treat more than 16 percent of Californians diagnosed with the disease. Of those, 45 percent are patients with late-stage cancers. In recent years, the pace of innovation in cancer therapy has become so rapid that the best care available is often obtained by joining a drug company-run trial of a drug headed for market. By joining together, the five UC cancer centers will optimize their resources and have the most immediately visible impact for diagnosed patients in the state. So far, the collaboration – comprising UCSF’s HDFCCC, UCLA’s Jonsson Comprehensive Cancer Center, UC San Diego’s Moores Cancer Center, UC Irvine’s Chao Family Comprehensive Cancer Center, and UC Davis’s Comprehensive Cancer Center – has built system-wide trials around head and neck cancers and blood cancers that might not have happened if only one cancer center were involved. The consortium of UC centers is a new model for cancer research and treatment. Dr. Ashworth indicated the model is a natural expansion in scope of the UC Hematologic Malignancies Consortium, launched in 2015, and comprising the five UC cancer centers to accelerate the testing of novel therapeutic agents in the treatment of blood cancers. “The new consortium will now help us address all cancer types,” he said. “Together we’re going to see the big picture of cancer in ways we never have before.”

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Rising Stars: New Faculty Members Lead to New Discoveries at UCSF The backbone of the HDFCCC is our incredible faculty, whose members collaborate across the entire UCSF campus, from the various research labs to the clinical offices in each division and department. Through these collaborations, young physician-scientists are mentored and supported in order to make valuable discoveries that move the science forward and pave the way for powerful new cancer treatments. Following are three of these remarkable individuals who are striving to make a positive impact in the lives of patients here at UCSF and around the world.

Sandy Wong, MD Finding ways to diagnose disease earlier and prolong survival Recruited to UCSF from Tufts Medical Center in Boston, Sandy Wong, MD is an integral part of the Grand MMTI team, where 80 percent of her patients have multiple myeloma. She specializes in studying light-chain amyloidosis, an extremely rare blood plasma cell cancer that affects approximately 4,000 new patients each year in the US. An expert on plasma cell diseases, Dr. Wong is intent on streamlining the diagnosis and treatment of light-chain amyloidosis and multiple myeloma.

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Unlike multiple myeloma, light-chain amyloidosis can be difficult to diagnose because the symptoms tend to mimic common disorders. For instance, many people in the US appear to have congestive heart failure or renal failure before being diagnosed with amyloidosis. Because the heart and kidneys are the most commonly affected organs, the diagnosis is often missed or not made until late in the disease when patients experience multiple-organ failure. “We work really closely together in the Grand MMTI, both clinically and in terms of translational research, to find new strategies to help our patients,” Dr. Wong says. “One of those strategies is to prolong survival rates of patients with light-chain amyloidosis. There are varying stages of the disease, with a typical prognosis of six months for those patients with late-stage cardiac disease.” Fortunately, Dr. Wong and her team members are working on a serum-free light-chain assay, an imaging technique that could assist in diagnosis. In patients with these plasma cell diseases, the malignant plasma cells overproduce a type of antibody, the components of which can be measured by this assay. There are fragments within the antibodies that act as surrogates for measuring the disease in the body and can assist in diagnosing the patient’s stage. “The serum-free light chain is considered part of a new standard of care, so we use this routinely at diagnosis and as the patients go through chemotherapy,” Dr. Wong says. “We check it regularly to monitor amyloid disease burden – the deposits in the body – over time and use it to see if we can predict organ response and therefore survival. Early diagnosis is key to a patient’s survival.”

Arun Wiita, MD, PhD Decoding cancer: modeling treatment resistance to overcome cancer In 2016, Arun Wiita, MD, PhD, received a National Institutes of Health New Innovator grant for pushing the boundaries of mass spectrometry technology to track the kinetics of protein-folding across thousands of different proteins in cells in near-real time. “There is a genetic basis for multiple myeloma that can be linked to progression and prognosis,” Dr. Wiita says. “Our research aims to better understand the genetics of disease and it influences cancer growth as mediated by proteins.” The immune system plays a central role in the prevention and treatment of multiple myeloma, a disease that Dr. Wiita researches as part of the Grand MMTI team. Early on, the immune system acts like a sentinel, detecting and destroying precancerous plasma cells before they can become malignant. However, if these precancerous cells evade the immune system and advance to

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full-blown disease, we now have therapies that can engage the immune system to again cause it to attack myeloma in those patients who have become resistant to current immunotherapies. “We’ve had a lot of great partnerships with local biotech companies that want to develop new myeloma therapeutics,” Dr. Wiita says. “Often they’ll come to the UCSF Grand MMTI team to collaborate and demonstrate efficacy of their exciting molecule in preclinical models of myeloma. Together, we determine whether we can make an investigational new drug application and actually put a new molecule in trials for UCSF patients.” Dr. Wiita’s lab uses mass-spectrometry technology in tandem with in vitro and in vivo mouse models to ascertain the efficacy of new drugs and their ability to locate and identify immunotherapy targets in the form of cell surface proteins. Previously, these targets on the cell surface were invisible with standard DNA or RNA sequencing. But now they can specifically isolate those proteins at the cell surface and study them through the use of mass spectrometry. Dr. Wiita and the Grand MMTI team are going one step further and creating models of resistance to known immunotherapies for myeloma. In this way, they hope to understand what changes occur at the cell surface and then use this model to explore how to overcome resistance. “Today we’re trying to make models of resistance to daratumumab, an effective immunotherapy for myeloma,” he says. “Even if patients become resistant to that one drug, we can predict how their disease will react to a different immunotherapy and target that after resistance occurs. In that way, we’ll always be one step ahead of myeloma.”

Rahul Aggarwal, MD Taking a STAND against prostate cancer Rahul Aggarwal, MD, director of the UCSF Supportive Therapy in Androgen Deprivation (STAND) Clinic, is an expert in using androgen deprivation therapy (ADT) as a standard treatment for patients with prostate cancer. Also known as hormone therapy, ADT is an extremely effective treatment for patients at various stages of the disease, including those with more advanced prostate cancer. However, ADT also causes side effects including fatigue, hot flashes, and decreased libido, to name a few.

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Genetic sequencing is integral to prostate cancer management in a way it wasn’t 10 years ago. We just have so much more we can do with the information now. Rahul Aggarwal, MD

Director, UCSF Supportive Therapy in Androgen Deprivation (STAND) Clinic

“A particular focus of mine was to set up a multidisciplinary clinic for men receiving hormone therapy,” Dr. Aggarwal says. “At the STAND Clinic, we are finding ways to improve upon ADT treatment and the side effects it can cause.” Some of the first of their kind, the UCSF STAND Clinics at Mount Zion and Mission Bay comprise experts in prostate cancer, psycho-oncology, symptom management, nutrition and exercise, all of whom work together to support men receiving ADT. Each patient receives a comprehensive, individualized treatment plan to manage the side effects associated with hormone therapy and can participate in clinical trials with the goal of developing new hormone therapies for prostate cancer. In addition to the STAND Clinic trials, Dr. Aggarwal is engaged in genomic sequencing studies, looking for mutations in targetable pathways including the DNA damage response pathways. Studies have shown that approximately 30 percent of advanced prostate cancer patients will have a mutation in one of these genes in their tumor sample. The good news is that there are medicines that target these same pathways, available through clinical trials or as standard-of-care. “We try to do genetic sequencing on as many of our advanced prostate cancer patients coming to the clinic as possible,” Dr. Aggarwal explains. “Genetic sequencing is integral to prostate cancer management in a way it wasn’t 10 years ago. We just have so much more we can do with the information now.” This year, Dr. Aggarwal helped design and run a national phase III trial to study and evaluate whether combination treatment will lead to a longer duration of disease suppression compared to standard ADT alone. The trial is under way at UCSF and other sites, and is expected to enroll more than 500 patients. “This trial is yet another way UCSF is applying precision medicine to try and enhance outcomes of standard hormone therapy like ADT for patients,” Dr. Aggarwal says. “We’re looking to not only suppress a cancer but also actually cure patients and eliminate their cancer resistance long-term.”

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With the aid of artificial intelligence, we hope to speed up the process to focus on prevention and treatment without having to wait for a biopsy to come back. Now with our Impact Grant Award funding, we have the resources to make that dream a reality much sooner. Maria Wei, MD, PhD

Maria Wei, MD, PhD, 2017 Impact Grant Award winner, with Michael Keiser, PhD (left), and Robert Judson, PhD.

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Director, UCSF Melanoma Surveillance Clinic

Impact Grant Awards: Bold New Approaches to Cancer Research In only two years, the Impact Grant Awards have already encouraged UCSF researchers to think bigger and develop bold new approaches to cancer research. This program spurs our young investigators to propose projects capable of great impact, as opposed to those with the greatest chance of receiving government funding.

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Maria Wei, MD, PhD; Robert Judson, PhD; and Michael Keiser, PhD Harnessing artificial intelligence and molecular diagnostics for rapid and accurate melanoma screening and diagnosis Melanoma, the most serious form of skin cancer, can be prevented. But using artificial intelligence to one day diagnose and prevent it? That’s the kind of nontraditional approach HDFCCC president Alan Ashworth encourages. “We acknowledge the fact that you might fail,” he said in his opening remarks at this year’s Impact Grant Awards event. “The only way you get big rewards is with big risk. This scheme is to try and do the not-blindingly-obvious and try something unusual that will make a big impact.” Maria Wei, MD, PhD, director of the UCSF Melanoma Surveillance Clinic, and her colleagues Robert Judson, PhD, Sandler Fellow in dermatology; and Michael Keiser, PhD, assistant professor in the Institute for Neurodegenerative Diseases, set out to do just that with their winning 2017 proposal. From a pool of 50 applications, Dr. Wei’s team was selected to develop a scanning tool for detecting melanoma, which has a 100 percent survival rate if found early. “The whole goal is to catch melanoma in the noninvasive stage or even a pre-melanoma stage, eliminating the need for a biopsy and going straight to treatment,” Dr. Wei said. The award brings $250,000 over two years to tackle their project’s two objectives. The first is image analysis using deep learning and artificial intelligence. The second involves marrying this technology with a biomarker to noninvasively diagnose and stage melanoma cancer. Preliminary data suggests that each of these techniques will work on its own, but it is the practical combination in an efficient and user-friendly diagnostic tool that Dr. Wei’s team is ultimately after. “I see patients with hundreds of moles because I’m looking at people at high risk for melanoma,” Dr. Wei says. “It’s incredibly time-consuming for the patient as well as the clinician. With the aid of artificial intelligence, we hope to speed up the process to focus on prevention and treatment without having to wait for a biopsy to come back. Now with our Impact Grant Award funding, we have the resources to make that dream a reality much sooner.”

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David Raleigh, MD, PhD, and Jeremy Reiter, MD, PhD

David Raleigh, MD, PhD; and Jeremy Reiter, MD, PhD Understanding how fat molecules can signal a cell to cause cancer Each cell in the human body, even those that do not make up fat tissue, contain fat molecules. Also known as lipids, these fats are involved in developmental and embryonic signaling pathways. One such pathway, known as the Hedgehog pathway given its somewhat spiky appearance, tells a cell when to divide during embryogenesis for the development of the lungs and brain, even ensuring a fetus has the right number of fingers and toes. But when these signaling fats go awry, they might tell a cell to overgrow, which can lead to cancer. If the error occurs in the Hedgehog pathway, it may lead to pediatric brain cancer. Through a collaboration with the UCSF Quantitative Biosciences Institute (QBI), David Raleigh, MD, PhD, assistant professor of radiation oncology; and Jeremy Reiter, MD, PhD, chair of the Department of Biochemistry and Biophysics, received the second 2017 Impact Grant Award for their work to find out how these Hedgehog pathways can instigate such deadly mutations. Drs. Raleigh and Reiter are working to better understand the key components of the Hedgehog pathway and how fat molecules interact with cilia, cellular antennae that sense cues from the outside world. Fat molecules use these single-strand antennae to signal the Hedgehog pathway and Drs. Raleigh and Reiter hope to fully map this process, to understand and possibly find a cure for pediatric brain cancer and other diseases. In their research, they have come across quite a unique and tasty compound that may prove to one day form the basis of a clinical trial for Hedgehog pathway-associated medulloblastoma, the most common type of pediatric brain tumor. That compound is licorice. “Jeremy and I discovered an enzyme that inhibits this pathway in cancer is from a naturally occurring compound in licorice,” Raleigh said. “Our research shows that when pharmaceutical-grade black licorice is administered to mice with tumors, the mice live longer and the tumors go away. You cannot make this stuff up.”

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” San Francisco Cancer Initiative: Uniting to Reduce Cancer Launched in November 2016, the San Francisco Cancer Initiative (SF CAN) is the first public-private cancer plan for a major American city, with an ambitious goal of reducing the rate of cancer among our nearly 875,000 residents using interventional strategies. This collaborative, innovative initiative aims to reduce mortality for one of the world’s most common diseases. As a pioneer in the field of precision population science, UCSF is leading the coordination and acceleration of these efforts. Task forces focusing on five of the city’s most common forms of cancer – breast, colorectal, liver, lung, and prostate – will use evidence-based prevention and screening practices that exist but are not being fully implemented across all communities. A comprehensive and integrated program is under way to put what is known about each cancer type into wide practice. The SF CAN is already having an impact in Northern California, with a first-of-its-kind ordinance to ban menthol cigarettes and flavored tobacco products within city limits up for a full-city vote in June 2018. “San Francisco’s size, population, and progressive culture make it an ideal place for an effort like this,” Dr. Ashworth says. “A cancer prevention model that works here could be applied to other cities in the years to come.”

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We’re at the beginning of this dialogue on global cancer, with the American Society of Clinical Oncology talking about it, too. UCSF is on the crest of this wave, and it’s very exciting. Katherine Van Loon, MD Assistant Clinical Professor and Oncology Specialist, Department of Medicine

Global Cancer Program: Looking Far and Wide to Advance Treatment Katherine Van Loon, MD, MPH A passion for her patients leads an oncologist far and wide Dr. Katherine Van Loon strives to provide her patients with the best quality health care. It’s why she decided to travel all the way from Boston to San Francisco and accept a fellowship in gastrointestinal oncology, her chosen field of interest. “UCSF has an amazing program in gastrointestinal oncology, with wonderful mentorship,” she says. “I’m part of a great group here that’s been the foundation of my medical career.” Traveling far and wide to learn best practices is also a passion of Dr. Van Loon’s; she completed rotations in South Africa through her MPH degree and during medical school and her residency. When she first came to UCSF in 2009, global oncology wasn’t yet considered an academic field. So Dr. Van Loon, who specializes in the treatment of colon and rectal cancers, worked on more conventional research projects and developed the gastrointestinal oncology survivorship clinic at UCSF, where her research focuses on personalized surveillance. It wasn’t until 2011, when the World Health Organization held a high-level meeting declaring an international emergency on non-communicable disease burden, that she had an opportunity to combine her two passions.

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The Muhimbili University of Health and Allied Sciences (MUHAS)-UCSF Esophageal Cancer Research Team is co-led by Dr. Katherine Van Loon (second from left) and Dr. Elia Mmbaga (second from right).

“I began the research phase of my fellowship around the same time an international dialogue began around the critical burden of non-communicable diseases, including cancer, impacting the developing world,” Dr. Van Loon says. “My first grant was to help Muhimbili University of Health and Allied Sciences in Dar es Salaam, Tanzania, to establish a population‑based cancer registry.” Dr. Van Loon dove into the data to describe the bizarrely high incidence of esophageal cancer in East Africa. While rare in the United States, esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related deaths. And in East Africa, it is one of the most common cancers among both men and women – for reasons nobody understands. “Known risk factors for esophageal cancer include smoking, obesity, and alcohol use,” she says. “But these are not common issues, and it definitely looks like there’s something else contributing to the high incidence of this cancer in East Africa. That’s been the exciting part of my research career. By going to high-incidence areas of these rare cancers, we’re able to accelerate our research.” Inspired by her newfound career path, Dr. Van Loon sat down with Dr. Ashworth to make a pitch for establishing a global oncology program as a field of study at UCSF. “Dr. Ashworth made global cancer a priority for the HDFCCC at a time when few recognized the extent of the problem,” she says. “After 15 minutes of my presentation, he stopped me and said, ‘OK, this is a no-brainer.’” Not long after their meeting, the UCSF Global Cancer Program – supporting multidisciplinary collaborations with low and middle income country partners – was established. Last September, Dr. Van Loon led a group of 10 UCSF senior trainees and faculty members to Tanzania for a weeklong symposium to establish broader cancer-focused collaborations. “One of our pathologists, Dianna Ng, MD, is now funded to do potentially groundbreaking breast cancer research there,” she says. “We’re at a pivotal moment in history. I remember being in Africa in 1991 when the HIV/AIDS pandemic seemed like an insurmountable challenge. Now, almost two decades later, I’ve found myself at the very beginning of establishing cancer control in low-resource settings. UCSF is uniquely positioned to respond to this issue.”

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We are advancing some revolutionary work, making conceptual leaps, and pushing the boundaries of what is known.

Adil Daud, MD

Director, Melanoma Clinical Research

From left: Lewis Lanier, PhD, American Cancer Society Professor, chair of the Department of Microbiology and Immunology, J. Michael Bishop, MD, Distinguished Professor in Microbiology and Immunology, and director of the UCSF center of the Parker Institute for Cancer Immunotherapy; Hope Rugo, MD, director of the Breast Oncology Clinical Trials Program; Adil Daud, MD, director of melanoma clinical research; and Larry Fong, MD, leader of the Cancer Immunotherapy Program and Efim Guzik Distinguished Professor in Cancer Biology, at UCSF’s 2017 Cancer Showcase.

Cancer Immunotherapy Program: Unleashing the Body’s Natural Defense Systems Immunotherapy has radically transformed outcomes for some patients with cancers deemed universally lethal just five years ago. These patients are living years in remission, and some ultimately may be cured. Currently, 20 percent of patients respond to immunotherapy, thanks to the ingenious work of pioneering scientists who are revolutionizing cancer treatment and visionary donors who are fueling the future of cancer care.

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The UCSF Cancer Immunology Program helps make immunotherapy effective in as many patients as possible across all cancer types. Under the direction of Lewis Lanier, PhD, and Larry Fong, MD, the Cancer Immunology Program seeks to innovate in the two major classes of immunotherapy: biologics (antibody therapies that can activate the immune system) and engineered immune cell-based therapies. “It’s unclear at this point which cancers are going to be best treated by these different types of immunotherapies,” Dr. Fong says. “That’s why we’re also investigating combination therapies such as traditional chemotherapy and radiation plus immunotherapy. All of it is in the works at UCSF.” In the hopes of improving patient outcomes across all cancers, UCSF researchers collect blood and tumor samples from patients enrolled in clinical trials and apply a host of different scientific analyses to investigate responses to therapy. The experiments are designed to determine why some immunotherapies currently seem effective only in certain cancers such as melanoma and lung, bladder, and kidney cancers. Dr. Lanier and his team are analyzing patient immune systems to see how immunotherapy treatment affects them, and to determine how the behavior of immune cells known as natural killer, or NK, cells differs among patients. They hope their findings will shed light on ways to use the same immunotherapies for other cancers and to develop new immunotherapies.

Kole Roybal, PhD Dr. Roybal is part of a new generation of cancer researchers using technology to engineer primary human T cells to recognize multiple antigens on tumors. These cells have receptors that detect and activate only in response to certain antigens and help overcome the immunosuppression that occurs within the tumor itself. The technology he’s developing could help eradicate certain treatment-resistant solid tumors, including lung and brain cancers, since solid tumors have many different mechanisms to prevent the immune response. Dr. Roybal is optimistic that in three to five years, small clinical trials will show that engineered immune cells can eradicate certain solid tumors that were previously highly resistant to treatment. “At the HDFCCC, we’re developing these new receptor systems that help immune cells detect the tumor,” he says. “The good news in immunotherapy is that the first CAR-T cells are being approved for hematological malignancies. That’s great to see. Now we want to build cell-based therapies that can make an impact in solid tumors.” Dr. Roybal hopes to counteract tumor defenses and build immune cells that can produce different therapeutics within a tumor and stimulate the immune response.

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One of the great things about working in the Grand MMTI is that we have a well-integrated team. It’s really my privilege to now be doing what I love at UCSF. Nina Shah, MD

Associate Professor, Department of Medicine

Nina Shah, MD In the race to find a cure for multiple myeloma, Nina Shah, MD, has spent her career studying natural killer (NK) cells. NK cells are part of the body’s own immune system, and are known to fight viruses and tumors. Dr. Shah has developed a way to expand them into a clinically useful dose. “We obtain the cells from umbilical cord blood, which is a readily available source, so we can infuse them into our patients as cell therapy against myeloma,” she says. While at the University of Texas MD Anderson Cancer Center, Dr. Shah and her colleagues developed a way to expand second-party NK cells – cells from a source other than the patient – to infuse as a therapy to kill myeloma. They were able to perform the first-in-human study of this protocol, enrolling 42 patients for two years of study and an additional year of follow-up. Now a member of the UCSF Stephen and Nancy Grand Multiple Myeloma Translational Initiative (MMTI) team, Dr. Shah is hoping her experience with cellular therapy will help her new team here. “One of the great things about working in the Grand MMTI is that we have a well-integrated team,” she says. “It’s really a privilege to be doing what I love at UCSF.” Dr. Shah and others have been able to take advantage of work done previously for treating melanoma and leukemia with immunotherapy agents and apply it to multiple myeloma. “We’ve recently had two classes of immunotherapies approved for leukemia and lymphoma: CAR-T cells and a bispecific T cell engager (BiTE). We’re studying these therapies for myeloma as well, and the FDA just announced approval of a CAR-T therapy for relapsed myeloma. It’s a really exciting time to be working in myeloma, particularly in immunotherapy. I’m just loving it.”

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Center for BRCA Research Opened in 2015, the Center for BRCA Research at UCSF is the first comprehensive clinic on the West Coast for individuals carrying hereditary gene mutations in BRCA1 or BRCA2, which are widely recognized as inheritable causes of breast and ovarian cancers. Only the second clinic in the nation to focus its clinical and research activities directly on BRCA mutations, the center concentrates on clinical care, screening and prevention (including a laboratory science program), education, and outreach to lead discovery of novel treatments and best practices. The Hereditary Cancer Clinic within the center has the capacity to treat 150 patients and conduct up to 100 genetic counseling sessions per month, with plans to expand staff and services to more BRCA-positive patients in the near future. The Center for BRCA Research was founded and is co-led by Dr. Ashworth and Pamela Munster, MD, professor of hematology and oncology, and is powered by their labs. Together, they conduct studies to screen for risk-modifying biomarkers that can identify carriers who are at high risk of developing cancer and who have the most potential for responsiveness to therapy. The Center for BRCA Research also works with community partners to develop and launch a regional public awareness plan. KinTalk.org, an educational and family communication portal where at-risk family members can securely share important hereditary genetic health information, is an important initial partner. From education to research to patient care, the center offers the most innovative and up-to-theminute information to the BRCA-positive community. According to Dr. Ashworth, this sets the Center for BRCA Research apart. “We plan to continue our work in each of the center’s core areas of focus, from growing our laboratory program and the Clinical Fellow Program to increasing the number of BRCA Challenge grants, in order to train future leaders in the field,” he says.

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Target Validation Initiative: The Key to Moving Novel Treatments Forward The UCSF Helen Diller Family Comprehensive Cancer Center aims to develop a novel cancer drug pipeline, translating the findings from its world-class cancer research into treatments addressing cancers, which currently have limited treatment options and poor outcomes. The Target Validation Initiative was developed to validate novel molecular targets, which are key to the development and progression of cancer and initiate drug discovery activities.

Current Projects I.

Target: HER-family Receptors Primary Investigators: Mark Moasser, MD, Professor, Department of Medicine (Hematology/ Oncology); Jack Taunton, PhD, Professor, Department of Cellular Molecular Pharmacology The project will accelerate medicinal chemistry optimization of a new lead series derived from the high-throughput screen thus far: 4-aminomethyl 2-aminothiazoles.

II. Target: Jumonji Demethylases Primary Investigators: Danica Fujimora, PhD, Associate Professor, Department of Cellular and Molecular Pharmacology; Brian Shoichet, PhD, Professor, Department of Pharmaceutical Chemistry This project will identify novel chemotypes of KDM4 inhibitors through a combination of molecular docking and molecule optimization followed by evaluation of potency and selectivity both in vitro and in cells. III. Target: uPAR Primary Investigators: Efrat Harel, MS, PhD, Post Doc, Department of Pharmaceutical Chemistry; Charles Craik, PhD, Professor, Department of Pharmaceutical Chemistry This project will target the urokinase receptor that is over-expressed in breast cancer for therapy.

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Thank You: Give Breast Cancer The Boot The last 20 years have seen a sea change in breast cancer treatment and outcomes. But with more than 40,000 women dying of breast cancer each year, there is still more to be done. Give Breast Cancer the Boot, a biennial fundraising event, gives UCSF researchers and clinicians an edge by supporting breast cancer research projects and programs. In 2016, more than 250 friends of UCSF attended the festive event to learn about the future direction of breast cancer research, enjoy great company, and listen to live music. They also raised a remarkable $1.1 million, which has contributed to 14 research projects and patient services. For example, UCSF provided nutrition counseling at the UCSF Carol Franc Buck Breast Care Center and massages for patients undergoing chemotherapy in the Ida Friend Infusion Center, services that have been very well received by patients. Additionally, “Boot” funding supports basic scientists focused on understanding the vulnerabilities of different types of breast cancers so we can better target them and improve outcomes. We’ve come a long way in the last 20 years in our understanding of breast cancer and how to personalize treatments for patients to achieve improved responses to therapies. At UCSF, our faculty and staff members embrace big ideas and transformative approaches that we hope will create breakthroughs for our patients and for patients everywhere.

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Š 2017 The Regents of the University of California Photographers: Steve Babuljak, Sonya Yruel E27532

UCSF Helen Diller Family Comprehensive Cancer Center Impact Report 2017–2018  
UCSF Helen Diller Family Comprehensive Cancer Center Impact Report 2017–2018