Inspired - Fall 2012 - University of Chicago Medicine

inspired fall 2012 / VOlUMe 3

A P H yS I C I A n P U B L I C AT I O n

at the ForeFroNt Pioneering scientists like Janet Rowley, MD, and her University of Chicago Medicine colleagues are transforming cancer treatment

BREAKTHROUGHS

New tool improves bladder cancer diagnosis InnOvATIOnS

Pediatric protocols for young adults RESEARCH

a trojan horse for brain tumors

ANNU

AL

ER CANC ISSUE

The University of Chicago medicine & Biological Sciences has been at the forefront of medical care, research and teaching for more than 90 years. Located in historic Hyde Park on the South Side of Chicago, the University of Chicago Medicine & Biological Sciences includes:

®

at t h e F o r e F r o N t o F M e d i c i N e

Patient care » Bernard A. Mitchell Hospital (adult) » Comer Children's Hospital » Duchossois Center for Advanced Medicine » Numerous outpatient locations throughout the Chicago area teaching Programs » Pritzker School of Medicine » Master's and doctoral degree programs » Postdoctoral programs research » Medical and basic science units Among our many honors and acknowledgements: 12 Nobel laureates; ranked 10th of all U.S. medical schools; one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers; ranked second in nation for National Institutes of Health grant support per researcher.

University of Chicago medicine & Biological

Pioneering scientists like Janet Rowley, MD, are the reason the University of Chicago Medicine is at the forefront in the battle against cancer, turning basic research from the laboratory into groundbreaking treatments at the bedside.

Sciences Executive Leadership kenneth s. Polonsky, Md, Dean of the University of Chicago Biological Sciences Division and the Pritzker School of Medicine,

DeaR cOlleaGUes,

and executive vice president for Medical Affairs for the University of Chicago

Few of us are not

In this edition of Inspired, we’d like to

touched by cancer,

introduce you to our rich history of

either through our

discoveries, the breadth of our ongoing

University of Chicago Medicine

own battles or those

clinical trials and the leading-edge

t. conrad gilliam, Phd, dean for

of family, friends and

technologies we’re using to detect and

patients. But each

treat cancer. We’d also like to highlight the

sharon o'keefe, president of the University of Chicago Medical Center richard baron, Md, dean for clinical practice,

research and graduate education, Biological Sciences Division holly J. humphrey, Md, dean for medical education, Pritzker School of Medicine iNsPired is PUbLished QUarterLY bY the UNiversitY oF chicago MediciNe & bioLogicaL scieNces.

day, physicians and scientists like Janet

expansion both on our Hyde Park campus,

Rowley, MD, who graces our cover, discover

where our state-of-the-art Center for Care

new reasons for hope as we struggle

and Discovery nears completion, and at

with this disease, its causes and its cures.

satellite sites such as the University of

editors Anna Madrzyk and Ginny Lee-Herrmann email us at: inspirededitor@uchospitals.edu design TOKY Branding + Design contributing writers Katie Scarlett Brandt, Tanya Cochran, John Easton, Elizabeth Gardner, Eileen Norris, Brooke O’Neill, Stephen Phillips, Gretchen Rubin, Anita Slomski and Shanna Williams contributing photographers Megan Doherty, Jean Lachat, Sandro Miller, Bruce Powell and Thomas Rossiter address the University of chicago Medicine 5841 S. Maryland Ave., Chicago, IL 60637 the University of chicago Medicine comer children's hospital

Chicago Medicine Comprehensive Cancer As a world-renowned academic medical

Center at Silver Cross Hospital, where we

center, the University of Chicago Medicine

recently added a pediatric oncology team.

prides itself on being at the forefront of this struggle, turning basic research

But, most of all, we’d like you to meet

from the laboratory into groundbreaking

Dr. Rowley and many of the others

treatments at the bedside. Our track

behind our success. Not only are they

record of success in translational medicine

among the best minds in cancer science

is one reason we’re the top-ranked

and medicine, they are among the best

cancer program in Illinois, according to

reasons for patients to feel confident

U.S. News & World Report, and one of only

about choosing the University of Chicago

two Chicago-area hospitals to carry the

Medicine for their cancer care.

National Cancer Institute’s top designation as a Comprehensive Cancer Center.

5721 S. Maryland Ave., Chicago, IL 60637 telephone 1-773-702-1000 appointments 1-888-824-0200 Follow the University of Chicago Medicine on Twitter at twitter.com/UchicagoMed or visit our Facebook page at facebook.com/ UchicagoMed. You can read more about our news and research at uchospitals.edu/news and at sciencelife.uchospitals.edu. this publication does not provide medical advice or treatment suggestions. If you have medical problems or concerns, contact a physician who will determine your treatment.

Do not delay seeking medical advice because of something you read here.

For urgent needs, call 911 right away.

Read Inspired online at uchospitals.edu/inspired.

KEnnETH S. POLOnSKy, mD Dean of the University of Chicago Biological Sciences Division and the Pritzker School of Medicine, and executive vice president for Medical Affairs for the University of Chicago

at the ForeFroNt oF caNcer care

A

B

CAnCER RISK & SURvIvORSHIP

BLADDER CAnCER

special Programs Focus on cancer Prevention, helping survivors

New imaging Method improves detection, helps Prevent recurrence

elizabeth noreen beat overwhelming odds in overcoming bone cancer that spread to her lungs when she was only 6 years old.

But the aggressive therapy that saved her life left the 21-year-old college student from Tinley Park, ill., with complex health challenges requiring careful management.

“We develop a care plan for each patient based on their prior treatments,” said Tara henderson, MD, MPh, noreen’s physician and director of the childhood, adolescent and Young adult cancer survivors center at the University

of chicago Medicine comer children’s hospital. henderson is an expert on the long-term effects of cancer treatment in childhood, including susceptibility to second cancers.

The center is one of several specialized programs in cancer prevention and survivorship at the University of chicago Medicine.

The cancer risk clinic helps people at risk for

breast, ovarian, colon, endometrial, pancreatic and other cancers. Patients work with counselors to develop a personalized action plan — diet and exercise, screening, medication or surgery — to mitigate their individual risk.

The Upper aerodigestive cancer risk clinic is a special program for people at high risk for the development or recurrence of lung cancer, head and neck cancer, esophageal cancer, mesothelioma and other malignancies.

The Pediatric Familial cancer clinic at the University of chicago Medicine comer children’s hospital helps children and families with an increased risk of cancer, including those with familial cancer syndromes. | B e l OW | tara henderson, Md,

MPh, and elizabeth Noreen

To improve treatment, start with a better diagnosis.

The University of chicago Medicine is the first hospital in the region to employ a diagnostic and assessment tool, known as cysview blue-light cystoscopy, that combines an fDa-approved fluorescent dye (hexaminolevulinate hcl) with a novel lighting system to better determine the extent of bladder cancers.

The standard diagnostic tool for suspected bladder cancer is “not as effective as we would like,” said Gary D. steinberg, MD, director of urologic oncology.

“That’s why we routinely repeat a cystoscopy and transurethral resection (TURBT) six weeks later, and 30 percent of the time we pick up new tumors on that second look.” in cysview blue light cystoscopy, 2 ounces of the fluorescent dye is instilled into the bladder through a catheter 60 to 90 minutes before cystoscopy and TURBT examination. The dye accumulates primarily in malignant cells. When illuminated with blue light from the cystoscope, those cells

| a B O V e | A: view of bladder under standard white light.

B: cancerous areas fluoresce bright red under blue light. courtesy of Photocure Usa.

fluoresce red, highlighting the malignant areas.

“When we switch from white to blue light, it’s like a big neon sign,” steinberg said.

“Tumor cells are calling out: ‘here i am.’”

This enables physicians to detect and resect bladder tumors more accurately than with standard white-light technology. “i find it extremely helpful,” said steinberg, who has used the technology in more than 70 cases. “it helps us do a better resection. We can see the satellite areas, often smaller tumors far from the original site. in addition, we can detect areas of carcinoma in situ that we could not readily identify with white light.”

The pivotal clinical trial, published in 2010, confirmed that blue-light cystoscopy significantly improves detection of bladder cancer, leading to a more complete resection and a 16 percent reduction in recurrence rates.

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Research News A TROJAn HORSE AGAInST BRAIn TUmORS

Tumors in the brain often are difficult to remove surgically without causing serious damage to surrounding tissues. Radiation produces side effects and only suppresses the tumor for so long. and the blood-brain barrier thwarts chemotherapy from reaching the brain. looking for ways to overcome these obstacles, scientists at the University of chicago Medicine and the city of hope comprehensive cancer center in california designed a sneak attack against brain tumors in animal models. The battle plan, according to University of chicago Medicine neurosurgeon Maciej s. lesniak, MD, involved loading an army of customized, tumor-killing viruses into an unusual vehicle: neural stem cells. These stem cells have the natural ability to seek out and target invasive brain tumor cells while leaving normal tissues unharmed. study results, published in Molecular Pharmaceutics, were promising, and the therapy is on track for clinical trials in humans within the next two years. The nih has committed more than $5 million for development of this therapy.

THE ASPIRIn EFFECT

in addition to lowering a person’s risk for heart attack and stroke, aspirin may prevent the development and progression of some cancers. a research team directed by radiation and cellular oncologist stanley liauw, MD, explored the association between aspirin use and prostate cancer recurrence and mortality in 6,000 men undergoing treatment. The study, published in the Journal of Clinical Oncology, found significant benefits for patients, especially those with highrisk prostate cancer. “The chance of dying from the disease was dramatically lower for patients who were on aspirin,” said liauw. he cautions that further studies are necessary before aspirin should be routinely recommended for prostate cancer patients. “a randomized study would be necessary to help weigh the potential risks and benefits of the therapy in men with prostate cancer,” liauw said.

LEARnInG FROm CELLULAR TRASH

GRAPEFRUIT JUICE DRUG BEnEFITS

Grapefruit juice has long been considered an overdose hazard, but a new study shows when used in a controlled fashion, the citrus drink can increase the efficacy of the drug sirolimus. in a paper published in Clinical Cancer Research, University of chicago Medicine researchers reported that grapefruit juice lets patients derive the same benefits from the anticancer drug as they would get from more than three times as much of the drug by itself. eight ounces a day of the juice slows the metabolism of sirolimus, which has been approved for transplant patients and may also help many people with cancer. study director ezra cohen, MD, says this combination could help patients avoid unpleasant side effects associated with high doses of this drug and reduce the cost of taking the medication.

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To thrive, cells regularly recycle or discard materials that no longer function effectively. called autophagy, this biologic mechanism is critical to the survival of cancer cells — and often is highly activated in these defective and continuously proliferating cells. a group of scientists led by University of chicago Medicine oncologist ezra cohen, MD, found that cancer cells’ sensitivity to a specific class of drugs was determined by how the cells went about “disposing of their trash.” in a followup translational research project, the team will combine existing therapy with autophagy inhibition to achieve cancer cell death and tumor remission. at the same time, the researchers will develop and test biomarkers to measure the state of autophagy in tumors, enabling clinicians to tailor therapy based on this fundamental susceptibility within a person’s cancer cells.

EXPLORInG An ESSEnTIAL vITAmIn

Vitamin D is known for its part in promoting calcium absorption and forming and maintaining healthy bones. Recent research has suggested the vital nutrient may also help prevent and treat disease, including cancer.

University of chicago Medicine scientists are investigating how vitamin D suppresses cancer on cellular and molecular levels. in a study published in the International Journal of Cancer, a team led by yan chun li, PhD, compared tumor growth in mice genetically engineered to express either normal vitamin D receptors (VDR) or inactivated VDR. The latter group grew larger intestinal tumors.

The authors determined that VDR’s signaling pathway suppresses colon cancer development. in a separate clinical study, the team is evaluating whether vitamin D supplements can prevent colon polyps in african-americans, who tend to have lower levels of serum vitamin D and higher incidences of colorectal cancer.

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JAmES K. LIAO, mD ,

is the new section chief of cardiology at the University of chicago Medicine. liao, an internationally recognized authority on blood vessel biology and arterial disease, was professor of medicine at harvard Medical school and director of vascular medicine research at harvard-affiliated Brigham and Women’s hospital.

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RICHARD L. SCHILSKy, mD , professor of medicine and chief of hematology/ oncology, is the 2012 recipient of the Pinedo cancer care Prize by the society for Translational Oncology. The award was established to honor the career of Professor Bob Pinedo in cancer research and compassionate patient care.

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ROSS mILnER, mD ,

associate professor of surgery and co-director of the University of chicago Medicine aortic diseases program, has been named the first Bucksbaum institute Master clinician. The Bucksbaum institute for clinical excellence at the University of chicago was established in 2011 to promote outstanding patient care, strong doctor-patient relationships and clinical teaching. Milner is honored for his clinical skills and judgment, excellent doctor-patient relationships, and teaching skills with students, residents and colleagues.

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KEnnETH S. POLOnSKy, mD , was among the top experts in various fields invited to contribute an article for the bicentennial issue of the New England Journal of Medicine. Polonsky is the Dean

InSPIRED to discover, teach & give back of the University of chicago Biological sciences Division and the Pritzker school of Medicine, and executive vice president for Medical affairs for the University of chicago. “The Past 200 years in Diabetes” appeared in the October 4 issue.

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JAmES L A BELLE, mD, PHD , has been named assistant professor of pediatrics. laBelle, a specialist in stem cell transplantation, was an attending physician in pediatric hematology/oncology at the harvard Medical school-affiliated Boston children’s hospital and Dana-farber cancer institute.

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LEILA KHEIRAnDISH-GOzAL, mD ,

from the american college of emergency Physicians. The award recognizes his outstanding contributions to education in the field of emergency medicine for the past three decades.

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Renowned cancer researcher received the 2012 icon innovator award from the illinois Biotechnology industry Organization institute for her work in identifying a chromosomal translocation as the cause of leukemia, paving the way for such targeted treatments as imatinib (Gleevec). Rowley is the Blum-Riese Distinguished service Professor of Medicine, Molecular Genetics and cell Biology, and human Genetics.

JAnET ROwLEy, mD ,

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SAmUEL L. vOLCHEnBOUm, mD,

director of pediatric clinical sleep research, and DAvID GOzAL, mD , physician-inchief at University of chicago Medicine comer children’s hospital, are the editors of a textbook, “sleep Disordered Breathing in children,” recently published by humana Press.

assistant professor of pediatrics and director of informatics for pediatric hematology/oncology, has been named associate director of the University of chicago institute for Translational Medicine.

Volchenboum will lead educational efforts, facilitate collaboration between researchers and oversee informatics research.

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University of chicago Medicine comer children’s hospital neonatologists now provide 24/7 coverage at community hospital in Munster, ind. KwAnG-SUn LEE, mD , chief of neonatology at comer children’s hospital, is the medical director.

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DAvID S. HOwES, mD , professor of medicine, received the Outstanding contribution in education award for 2012

coLorectaL caNcer screeNiNg iNitiative

Working to overcome barriers to breast cancer treatment in Nigeria

The University of chicago Medicine has partnered with the american cancer society illinois Division in a statewide initiative to increase colorectal cancer awareness and screenings in at-risk populations, including members of the africanamerican and asian-american communities on chicago’s south side.

liese Pruitt, a third-year student at the University of chicago’s Pritzker school of Medicine, recently visited ibadan, nigeria, for the second time to study social and cultural barriers that cause women there to delay treatment for breast cancer.

Pruitt, whose research was funded by the Dennis lee and anita cheng lee Global health scholarship, thinks there are ways

PHD, mS ,

The cancer Research foundation selected KEnAn OnEL, mD, PHD , associate professor of pediatrics, and ERnST LEnGyEL, mD, PHD , professor of obstetrics and gynecology, as 2012 fletcher scholars. The fletcher awards were created to fund the work of individual senior cancer scientists.

to cut through misinformation about breast cancer and get women care sooner. she hopes to pilot an education program by collaborating with clerics to urge women to seek medical care in addition to spiritual healing when they find a breast lump. “liese’s work has opened new opportunities for interventions to improve breast cancer outcomes in low-resource settings,” said Olufunmilayo i. Olopade, MD, director of the cancer Risk clinic at the University of chicago Medicine.

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collabrx: Database uses genetic information to match patients, therapies As a physician-scientist, Ravi Salgia, MD, PhD, understands the value of putting leading-edge research findings quickly into the hands of fellow oncologists.

“When I started my career two decades ago, the research and clinical worlds were quite separate,” he said.

“There was no big integration of the scientific information with the clinical information.”

Now, he’s helping to bridge the gap. The University of Chicago Medicine oncologist is senior editor for the lung cancer section of CollabRx (collabrx.com), an innovative, multi-institution online database that connects physicians and patients to promising clinical trials and therapies, all based on genetic information about their tumors. It currently covers lung, colorectal and melanoma cancers.

After the user plugs in diagnostics about the tumor, including type, stage and sites of metastasis, the targeted therapy finder provides a list of clinical trials around the country, therapies and related scientific literature.

“It’s a very novel approach to doing things, because it provides a go-to website for physicians or patients and families seeking better options,” Salgia said. Free to use and open to the public, the year-old site is already helping health care providers and their patients reach more informed decisions — and more promising outcomes.

traNsLatiNg todaY’s discoveries Laboratory discoveries by University of Chicago Medicine scientists are leading to a better understanding of the biological basis of cancer and personalized therapies

Leading-edge research targets lung cancer in the wild, C. elegans is practically invisible.

Barely a millimeter in length, these microscopic worms burrow in soil and compost heaps, feeding on bacteria from decaying produce. yet in thoracic oncologist Dr. Ravi salgia’s laboratory at the University of chicago Medicine, they’re helping pave the way for more personalized cancer treatments.

“C. elegans turned out to be a very powerful tool,” said salgia, MD, PhD, who has spent the past decade pinpointing genetic mutations that occur in lung cancer tumors. By implanting a human transgene in the worm and observing its effects, his team can more quickly determine which of those abnormalities make promising drug targets. it’s a pioneering experimental setup that often takes only a few weeks, versus the year or more required for more traditional mouse models.

“What we like are better answers faster,” said salgia, MD, PhD, vice chair for translational research in the Department of Medicine. as a researcherclinician, that means speeding up the process of bringing genetics-based lab discoveries to patients.

The mutations he’s analyzing in C. elegans today may lead to the novel therapies of tomorrow. salgia’s efforts, together with those of the university-wide institute for Translational Medicine and the University of chicago Medicine comprehensive cancer center, are creating a future of care where every treatment targets a tumor’s precise Dna.

“from years of research done at the University of chicago and elsewhere, we have learned that each person’s tumor is unique,” explained Richard l. schilsky, MD, hematology/oncology section chief.

“Our goal is to understand what makes a patient’s tumor tick at the molecular level and, based on that knowledge, deliver the best available therapy for that individual.” in his clinic, for example, salgia recently treated a lung cancer patient whose tumor had metastasized.

Rather than starting chemotherapy, once standard for stage 4 lung cancer, he ran a molecular analysis of the tumor and discovered that a rare genetic mutation called an alK translocation was fueling the cancer cells.

“There’s a specific targeted therapy that works against that translocation,” explained salgia, who spearheaded clinical trials for the drug at the University of chicago in 2010. The therapy, now salGia known as crizotinib, was approved by the food and Drug administration in august 2011 and is just one example of how University of chicago Medicine patients often receive access to genetic-based treatments before they are available elsewhere.

“We take pride in taking care of our patients,” said salgia, “but we also take pride in making sure we can do state-of-the-art research and then combine the two to provide even better care.”

That’s why with every tumor he studies in C. elegans, salgia increases the likelihood of better clinical outcomes down the road. “if we can do more for our patients from the research perspective,” he said, “then we’ll be able to do more from a clinical perspective.”

For more information, visit uchospitals.edu/ physicians/ravi-salgia.html.

iNto toMorroW’s treatMeNts collaborating on an innovative approach to chemo-resistant breast cancer

“Mifepristone is an Fda-approved medication used for emergency contraception. Mifepristone, however, is also a powerful blocker of gr activity,” Nanda explained. “the goal of our study is to see if combining mifepristone with standard chemotherapy can improve outcomes for patients with advanced breast cancer.”

resistance to conventional treatment is a roadblock that most patients with metastatic breast cancer face. the situation leaves few alternatives for treatment, but a novel approach now is in clinical trials at the University of chicago Medicine.

to support this work, Nanda and conzen applied for funding from the University of chicago’s institute for translational Medicine (itM). in November 2011, Nanda’s project was awarded funding to begin a phase 1 clinical trial to determine the appropriate dose of mifepristone to combine with the standard chemotherapy drug nab-paclitaxel (abraxane).

the collaboration between physicianscientist suzanne d. conzen, Md, and clinical researcher rita Nanda, Md — both experts in the diagnosis and treatment of breast cancer — stems from conzen’s groundbreaking research on signaling pathways and their role in cancer.

Nanda enrolled the first patient in the study in January 2012, and to date a total of eight patients have joined the study. conzen and Nanda were recently awarded a $675,000 grant from the susan g. komen Foundation to further this research. this grant will allow the investigators to study the effects of gr on chemotherapy effectiveness, namely in patients with triple-negative breast cancer.

conzen, who has been studying chemotherapy resistance since opening her lab in 1998, observed that the stress hormone cortisol activates the glucocorticoid receptor (gr) pathway and contributes to chemotherapy resistance in a subset of breast cancers. a meta-analysis of published studies revealed that the gr is overexpressed in 40 percent of advanced breast cancer cases. this led conzen to theorize that tumor activation of the gr protected some cancer cells from cell death and ultimately made them resistant to chemotherapy. conzen and Nanda designed a trial to test this hypothesis in patients with advanced breast cancer.

“the ultimate goal of our study is to improve outcomes for patients with advanced breast cancer,” Nanda said. “if we can do that while maintaining quality of life, then we will have accomplished something incredibly significant.”

cOnZen

nanDa

CLInICAL TRIAL ELIGIBILITy

This trial is one link in a long-standing research effort examining connections between stress and cancer.

Referral of any qualified patients who may be interested in participating is appreciated, and progress will be reported.

KEy ELIGIBILITy REqUIREmEnTS InCLUDE:

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Metastatic or locally advanced unresectable breast cancer

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evaluable disease

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Up to four prior cytotoxic regimens for advanced breast cancer

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No prior nab-paclitaxel for metastatic disease

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Peripheral neuropathy ≤ grade 1

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No need for corticosteroid therapy

Questions about the protocol may be directed to Jean gibson, rN, at 1-773-834-2167.

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for more than 70 years at the University of chicago Medicine, the brightest minds in medicine have been changing how physicians and scientists think about, diagnose and treat cancer

The eVOlUTiOn Of canceR Anjuli Nayak, MD, of Bloomington, Ill., survived an aggressive form of leukemia because of a cancer treatment sparked by a scientific breakthrough 40 years ago in a University of Chicago laboratory. Janet Rowley, MD, discovered the first recurring chromosomal abnormality linked to cancer.

That eventually led to the development of targeted therapies for cancer, including the drug that helped save Nayak’s life.

PAST Janet Rowley, MD, changed the way scientists think about and treat cancer. in 1972, she discovered the first translocations in human cancer cells, opening the door to effective targeted therapies. at 87, Rowley is an active cancer researcher at the University of chicago Medicine, where her work focuses on the consequences of chromosomal translocations on gene expression in leukemia cells.

Rowley is the recipient of many prestigious awards, including the Presidential Medal of freedom, the highest civilian honor bestowed in the U.s., and a mentor to future groundbreaking physician-scientists.

see Nayak’s story on page 8.

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wHAT IS IT ABOUT THE UnIvERSITy OF CHICAGO mEDICInE THAT InSPIRES SCIEnTISTS?

The environment allows for exploration of potentially groundbreaking, translational scientific theories. it provides a great deal of freedom to investigators, and i never was told what to do in the laboratory. i was asked to collaborate with people, and the collaborations were with very intelligent and dedicated physicians and scientists. They encouraged me to continue my line of research. wHAT IS THE mOST EXCITInG/ PROmISInG AvEnUE OF CAnCER RESEARCH TODAy?

The molecular genetic analysis of tumor cells will provide information we need to move toward effective tumor-specific

HORmOnE THERAPy CHEmOTHERAPy

hormone therapy is a mainstay of treatment for several types of cancer, including prostate and breast cancer.

Many cancer drugs still in use are derived from nitrogen mustard.

TODAy

TODAy

1939

1943

charles b. huggins, Md, uses hormone therapy to treat a patient with prostate cancer. he was awarded the Nobel Prize in 1966.

treatment. Gleevec and cMl are among the most outstanding examples, but new strategies for identifying critical genes driving the malignant behavior of individual tumors are important. new research identifies different aspects of the normal organization of genes and regulatory factors in Dna. These reports will substantially increase our understanding of gene interactions and will help us identify more precisely which changes are significant in a tumor cell. Genetics is important in all human diseases — cardiac, pulmonary, diabetes — and the University of chicago Medicine is leading the way. wHAT DOES THE CAnCER RESEARCH HAPPEnInG HERE mEAn FOR PATIEnTS?

Many scientists are not only working to identify abnormal genes in cells from cancer patients, but also more effective therapies. i go back to my own discovery of the translocation in cMl, which led to the identification of the genes at the translocation’s breakpoints.

Gleevec is a drug that targets one of those genes and has transformed the way we treat patients with cMl and other types of cancer. This is an example of how research at the University of chicago Medicine has and will continue to improve the lives of patients.

Leon Jacobson, Md, is the first to study the effectiveness of the chemical nitrogen mustard for terminally ill patients with leukemia and lymphoma. the University of chicago is considered one of the birthplaces of cancer chemotherapy.

| l e f T | Janet

rowley, Md, is a cancer researcher at the University of chicago Medicine and a mentor to future groundbreaking physicianscientists. her discovery of the first recurring chromosomal abnormality associated with cancer led to development of the first targeted therapy.

BOnE mARROw TRAnSPLAnT GEnETIC BASIS OF CAnCER

The University of chicago Medicine’s innovative approach makes transplants possible for patients who do not have a standard match and for high-risk patients.

Gleevec is used in the treatment of several cancers, including leukemia, lymphoma and gastrointestinal stromal tumor (GisT).

TODAy

TODAy

late 1940s

1972

Leon Jacobson, Md, performs the first bone marrow transplant on a mouse. twenty years ago, the University of chicago Medicine started the first pediatric bone marrow transplant program.

Janet rowley, Md, discovers the first recurring chromosomal abnormality associated with cancer, demonstrating that cancer is a genetic disease. her research led, decades later, to the development of gleevec (imatinib), the first, and most successful, targeted cancer therapy.

PRESEnT although she is a physician, anjuli nayak, MD, had never been on an oncology unit. she realized that was going to change the moment she learned a routine blood test showed her white blood cell count was 22,000. “i wasn’t sick, and i didn’t have any symptoms, but i knew i had leukemia,” said nayak, an allergist-immunologist with a practice in Bloomington-normal, ill. after researching treatment programs around the country, nayak made an appointment with Wendy stock, MD, a hematologist-oncologist at the University of chicago Medicine and a nationally known authority on leukemia. nayak was diagnosed with acute lymphoblastic leukemia (all) and tested positive for the Philadelphia chromosome mutation. | B e l OW | Leukemia patient anjuli Nayak, Md, right, and her physician, Wendy stock, Md

University of chicago researcher Janet Rowley, MD, identified the first recurring chromosomal abnormality associated with leukemia, laying the groundwork for the development of imatinib (Gleevec) and other targeted therapies. nayak’s initial therapy included a combination of traditional chemotherapy as well as dasatinib (sprycel), a second generation of imatinib. introduced in 2006, dasatinib specifically targets Philadelphia chromosome-positive all. The University of chicago Medicine was among the first centers in the country to test both of these highly effective medications.

The medical team felt a stem cell transplant offered nayak the best chance for a cure.

Because a fully matched donor was not available for her transplant, nayak was offered an opportunity to enroll in a clinical trial involving transplantation of stem cells from both a half-match donor and from donated umbilical cord stem cells.

“This approach allows us to make transplant available to patients who do not have complete immunological matches,” stock said. “The half-matched (haploidentical) stem cells engraft quickly and produce blood cells for a limited time.

They provide the bridge needed to allow the umbilical cord cells to take hold for

8 » THE UnIvERSITy OF CHICAGO mEDICInE InSPIRED mAGAzInE | FALL 2012

“This approach allows us to make transplant available to patients who do not have complete immunological matches.” wEnDy STOCK, mD

the long term. During the trial, we saw a seamless transition of haploidentical to cord engraftment.” in December 2011, stock and other University of chicago Medicine investigators published a paper on the first 45 patients in the U.s. to undergo this type of transplantation. in addition to quick engraftment, study results showed low risk of graft-versus-host disease (GVhD) and lasting remissions in many high-risk patients. nayak, who received her half-match cells from her middle son, then a medical student, was among the initial group of patients in the trial.

Today, nayak continues to take dasatinib daily and has no measurable evidence of lingering leukemia. “i am so grateful to the leukemia transplant team for the care, compassion and courage received from the doctors and nurses,” nayak said. “They have given me a rebirth, for which i am eternally grateful.”

PERSOnALIzED TREATmEnT

University of chicago Medicine researchers are working to develop personalized, targeted therapies for cancer based on the patient’s — and the tumor’s — genetic makeup.

yUSUKE nAKAmURA, mD, PHD

TODAy

FUTURE

“i would like to cure cancer.”

2010 the University of chicago Medicine center for Personalized therapeutics opens. director Mark J. ratain, Md, and deputy director Yusuke Nakamura, Md, Phd, one of the world’s top experts on pharmacogenomics, lead the efforts to translate genomic discoveries into improved care for patients.

FUTURE new genomic research shows that all the cells in a tumor are not alike, but are similar to animal or plant populations in the genetic variation they display. That variation is key to understanding what makes cancers return or appear in other parts of the body after treatment. University of chicago Medicine researchers are sequencing the genomes of individual cancer cells to discover ways to exploit genetic variations and eradicate — or at least tame — a given cancer.

“We might just be able to manage it like a chronic disease,” said Marsha Rosner, PhD, chair of the university’s Ben May Department for cancer Research and a senior fellow at the institute for Genomics and systems Biology, a collaboration between the University of chicago and argonne national laboratory. “The goal is to put your finger on two or three drugs that can keep it tamped down.”

Rosner’s breast cancer research focuses on transient changes in cellular patterns that can contribute to eventual mutations. such changes often are caused by environmental factors, including cancer treatments themselves for the low percentage of cancer cells that typically survive them. she studies both the genetics of the cells and the

epigenetics — the activity of the parts of Dna that lie outside the genes but determine whether and how the genes are expressed.

“We have to look at cells individually to study these things,” Rosner said. “Up until now we’ve treated tumors as homogeneous masses. now the technology is good enough that we can sequence single cells, and we are realizing there’s a big distribution and there are cells that have more mutations.”

Two other University of chicago Medicine researchers, pediatric hematologistoncologist Kenan Onel, MD, PhD, and molecular geneticist chung-i Wu, PhD, are using population genetics to study

variation in tumor cells. Wu, a professor in the University of chicago Department of ecology and evolution, also holds an appointment at the Beijing institute of Genomics. The Beijing institute’s genesequencing firepower and critical mass of genetic scientists complement the University of chicago Medicine’s patient data and ability to get patient samples.

Onel says the same mechanisms of natural selection that apply to animal and plant populations also apply to the cell populations found in tumors. While some mutations may be caused by chemotherapy, many already exist and allow their cells to survive the treatments. Onel focuses on acute lymphoblastic leukemia. Wu has been studying hepatocellular carcinoma, the most common type of liver cancer. he and Onel have been collaborating to figure out which genetic variations survive cancer treatment and why. “if we can model [the emergence of drug resistance], maybe we can prevent it,” Onel said. “We may be able to change core pathways inside the cell that control Dna damage or repair. We need to let the cancer itself tell us what’s important to it.”

For more information about cancer breakthroughs at the University of Chicago Medicine, visit uchospitals.edu/cancer. kenan onel, Md, Phd

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CME & edUcatioNaL oPPortUNities

FInD A CAnCER EXPERT nEAR yOU +

26th annual conference: challenges for clinicians nOvEmBER 30 — DECEmBER 2

Drake Hotel 140 E. Walton Place, Chicago CO-DIRECTORS Avery Tung, MD,

director of critical care services, University of Chicago Medicine Burn Unit, and Jeffrey L. Apfelbaum, MD, chairman of anesthesia and critical care

steMi 2012: treatment options and Management for the complex Patient 2nd annual Update on steMi and acute coronary syndromes DECEmBER 1, 7:30 Am — 1 Pm

University of Chicago Gleacher Center, Room 621, 450 N. Cityfront Plaza Drive, Chicago CO-DIRECTORS Atman P. Shah, MD, director, Coronary Care Unit, and Sandeep Nathan, MD, MS, director, interventional cardiology research and education and Interventional Cardiology Fellowship Program

15th annual conference: challenges for clinicians JAnUARy 21 — 26, 2013

The Westin Resort St. John, Virgin Islands CO-DIRECTORS Avery Tung, MD, and Jeffrey L. Apfelbaum, MD

THE UnIvERSITy OF CHICAGO

CO-DIRECTORS Martin C. Burke, DO,

mEDICInE COmPREHEnSIvE CAnCER

director, Heart Rhythm Center, and Joshua D. Moss, MD, cardiac electrophysiologist

CEnTER at Silver Cross Hospital,

advanced treatment options in heart Failure mARCH 9, 2013, 6 — 9 Pm

The Fairmont San Francisco 950 Mason St., San Francisco, Calif.

CO-DIRECTORS Martin C. Burke, DO; Allen S. Anderson, MD, director, Advanced Heart Failure Program, and medical director, cardiac transplant services; and Savitri E. Fedson, MD, cardiologist

New Lenox, Ill., provides multidisciplinary, comprehensive cancer care for adult and pediatric cancers. our leading-edge cancer care also is available at additional locations throughout the region:

+

PEDIATRIC CAnCER CARE Edward Hospital, Naperville, Ill., and in Palos Heights, Ill., and Merrillville, Ind.

+

+ Mark YoUr caLeNdar:

valvular/tavr/ thoracic aortic disease mAy 2013 CO-DIRECTORS Roberto M. Lang, MD, director, cardiac imaging, and Marion Hoffmann-Bowman, MD, PhD, cardiologist

University of Chicago Medicine physicians are available to present in-office CME courses in greater Chicagoland and Northwest Indiana.

For information, please contact Carrie Sota, carrie.sota@uchospitals.edu.

Register for CME events at cme.uchicago.edu.

advances in therapy to Prevent sudden death JAnUARy 26, 2013, 8 Am — 2 Pm

University of Chicago Medicine Center for Care and Discovery, 7th floor, 5700 S. Maryland Ave., Chicago

10 » THE UnIvERSITy OF CHICAGO mEDICInE InSPIRED mAGAzInE | FALL 2012

GynECOLOGIC OnCOLOGy

Silver Cross Hospital, New Lenox, Ill., and University of Chicago Health Specialists, Schererville, Ind. RADIATIOn OnCOLOGy

Sherman Hospital Cancer Care Center, Elgin, Ill. AT THE FOREFROnT

10 GOInG UP! The 10th floor of our new hospital is devoted to cancer care, including a bone marrow transplant unit.

The University of Chicago Medicine Center for Care and Discovery opens in early 2013.

Ask the Expert Mi c h e ll e M. l e B e aU , Ph D

the University of chicago Medicine comprehensive cancer center is one of just 41 hospitals in the nation — and only two in illinois — to earn the “comprehensive” designation from the National cancer institute (Nci). q: HOw DOES An InSTITUTIOn EARn THE nATIOnAL CAnCER InSTITUTE “COmPREHEnSIvE” DESIGnATIOn?

The designation recognizes scientific excellence and an institution’s dedication to developing more effective approaches in cancer care through research. To qualify, a cancer center must demonstrate depth in basic, clinical and population-based research, as well as collaborative, transdisciplinary research bridging these areas. The nci also requires the center to provide cancer training to medical professionals, and education and outreach to the community, with an emphasis on underserved populations. The designation must be renewed every five years.

A:

q: wHAT IS THE mISSIOn OF THE UnIvERSITy OF CHICAGO mEDICInE COmPREHEnSIvE CAnCER CEnTER?

Our mission is to elucidate the determinants of cancer, to find cures for cancer and to prevent cancer. We have long been recognized for our major contributions in defining the molecular mechanisms that give rise to cancer, conducting innovative clinical trials and developing new therapies.

We are one of only a few institutions in the country that conducts nci-sponsored A:

phase 1, phase 2 and phase 3 trials. Through 320 open therapeutic clinical trials, we offer the newest treatment approaches to our patients. q: wHAT ELSE DISTInGUISHES THE UnIvERSITy OF CHICAGO mEDICInE COmPREHEnSIvE CAnCER CEnTER?

We are transforming the routine practice of medicine by leading efforts to personalize cancer care. Through our center for Personalized Therapeutics, we are leading the way in implementing pharmacogenomics into clinical trials and daily practice, enabling our physicians to tailor the most effective treatment plan for each patient.

We are also using genetics to improve our knowledge of cancer susceptibility, development and progression, as well as treatment and prognosis. additionally, we have devised a central intake and navigation system to streamline and improve the health care process for our patients, and our cancer survivorship programs bring together multidisciplinary experts to address the unique medical and social needs of our survivors.

A:

q: wHAT’S nEXT FOR THE CAnCER CEnTER?

We are looking forward to the opening of our new hospital in early 2013, the University of

A:

chicago Medicine center for care and Discovery, which will expand our capacity to provide personalized cancer care to our patients. Over the next five years, we are embarking on an ambitious strategic plan that aims to expedite the translation of research discoveries into personalized care, and to ensure that these innovations are incorporated into standard medical practice and accessible to all populations.

To meet this challenge, we are developing a new center for cancer Prevention and Population Research to study the determinants and risk factors of cancer and build new disease prevention programs.

We have also developed a Personalized cancer care consortium to enroll patients in clinical trials to test new cancer interventions developed in the laboratory. finally, an expanded program focusing on cancer outcomes and survivorship will address the challenges of cancer survivors as well as improve outcomes and steward our health-care resources to maximize benefit to our patients.

MicheLLe Le beaU Michelle M. Le beau, Phd, a leading authority on hematological malignancies, is director of the University of chicago Medicine comprehensive cancer center.

Le beau also holds a national leadership position as the president of the association of american cancer institutes, which represents 95 of the nation’s premier academic and freestanding cancer centers.

For more information, visit cancer. uchicago.edu.

AT THE FOREFROnT

210

LABORATORY AND CLINICAL SCIENTISTS FOCUSING THEIR EFFORTS ON CANCER

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caNcer treatMeNt & cLiNicaL triaLs Young adults with blood cancer: Why it’s better to treat them Like kids When caring for adolescents and young adults (ayas) who have leukemia, cancer specialists at the University of chicago Medicine now tailor pediatric therapy to fit this distinctive group of patients.

The recent transformation in how ayas are treated came as a result of scientific investigation and clinical trials. in 2008, University of chicago Medicine physician-scientists conducted a retrospective study comparing survival rates for 300 acute lymphoblastic leukemia (all) patients, ages 16 to 20, who had been on either pediatric or adult protocols. | a B O V e | Jenn georges, 24, was the first patient seen in the new aYa clinic at the University of chicago Medicine.

“The study demonstrated 63 percent disease-free survival for young adults on pediatric trials versus 39 percent for those on adult trials,” said Wendy stock, MD, a leukemia expert and lead author of the study published in Blood. following this observation, three adult oncology groups in the nation collaborated on a clinical trial to further test a pediatric approach for all patients, ages 16 to 39.

The ongoing study also is examining the factors that influence participation in — and compliance with — the intensive therapy.

Diagnosed with all soon after graduating from college downstate in 2009, Jenn Georges returned home to get her care at the University of chicago Medicine.

AT THE FOREFROnT

she enrolled in the clinical trial after stock explained it could give her the best chance at survival.

Despite the rigorous regimen, Georges earned her master’s degree online and started a new job while undergoing chemotherapy. now the 24-year-old is busy planning her upcoming wedding. With her adult life on track, Georges doesn’t mind that when it came to fighting leukemia, she was treated — in one way — like a child. nEw CAnCER PROGRAm DESIGnED FOR yOUnG ADULTS

The new adolescent and young adult (aya) Oncology Program at the University of chicago Medicine offers diagnostic, treatment and support services for young adults (ages 15 to 30) with leukemia or lymphoma. as leaders in aya cancer research, we have access to the latest clinical trials and protocols for this patient population. The clinic’s multidisciplinary medical team includes adult and pediatric hematologist-oncologists, advanced practice nurses and social workers, as well as specialists in survivorship, psychology, fertility and genetics.

The aya Oncology Program sees patients in the comer center for children and specialty care, a new state-of-the-art outpatient clinic and infusion suite adjacent to the University of chicago Medicine comer children’s hospital on the medical center’s hyde Park campus.

For more information about the AYA Oncology Program, visit uchospitals.edu/ specialties/cancer/young-adult.

AT THE FOREFROnT

NUMBER ONE #1 cancer center in illinois in U.S. News & World Report’s 2012 rankings

12 » THE UnIvERSITy OF CHICAGO mEDICInE InSPIRED mAGAzInE | FALL 2012

320

canceR clinical TRials

clinical trials Move cancer treatment Forward The University of chicago Medicine comprehensive cancer center is one of the few institutions in the nation that conducts national cancer institutesponsored phase 1, phase 2 and phase 3 clinical trials. By designing and conducting innovative clinical trials, we are able to offer the newest treatment approaches to our patients.

“Besides getting the best standard of care, there’s also the potential for getting tomorrow’s standard of care,” said Walter M. stadler, MD, associate dean for clinical research at the University of chicago Medicine and director of the genitourinary program. stadler recently examined a patient who was enrolled six years ago in a clinical trial for a new therapy for renal cancer. That medication now is the approved, ongoing standard of care. “This patient received the drug as part of a clinical trial years ago and continues to do well today,” he said.

The University of chicago Medicine has 320 clinical trials for cancer. Patients enrolled in clinical trials benefit from being closely followed by an expert team, including physicians, researchers and other specialists. Many patients are pleased that their participation in a clinical trial is likely to help future patients diagnosed with cancer.

The best way to access the clinical trial system is through a cancer intake coordinator.

For more information about cancer clinical trials at the University of Chicago Medicine, go to uchospitals.edu/clinical-trials.

L A C E Y ’ S S TO RY:

the giFt oF LiFe LACEy’S STORy InSPIRES BOnE mARROw DOnORS, COnTRIBUTIOnS TO RESEARCH

The bond between lacey horwitch and her father, David, runs much deeper than the typical father-daughter relationship. When the 9-year-old was diagnosed with two very rare disorders, one of which causes the body to attack its organs, she desperately needed a blood stem cell or bone marrow donor.

Determined to find a match, her family partnered with numerous organizations to hold bone marrow donor drives near their home in northbrook, ill. With no success and lacey’s condition quickly deteriorating, her father — who was just a 50 percent match — donated his stem cells, offering lacey the lifeline she needed.

since the bone marrow drives, at least four people have been contacted by the national bone marrow registry as potential matches for sick patients. “i look at it as lacey has saved three or four lives by these drives, which otherwise would not have happened,” said lacey’s mother, laura horwitch.

When they’re old enough to be eligible, lacey’s sisters, Maya, 11, and Jenna, 6, will register to become donors themselves. in the meantime, laura says the family is simply focused on never taking a moment for granted.

her spirit and energy keep us going. This was a wake-up call to appreciate every moment of life.

LAURA HORwITCH

“she’s had some transplant complications, but we believe she’s going to overcome those hurdles,” said David, a chicago-based attorney.

The University of chicago Medicine comer children’s hospital is one of the only centers in the Midwest offering stem cell transplants from parents, made possible by stateof-the-art cell purification technologies. The little girl’s family credits renowned experts John cunningham, MD, chief of pediatric hematology/oncology, and Roy e. Weiss, MD, PhD, chief of adult and pediatric endocrinology, diabetes and metabolism, with saving lacey’s life. “all the medical staff was very committed and dedicated to their work,” said David. “We found the doctors to be accessible and responsive.” in recognition of the care she received and wanting to give back, the horwitch family hosted several fundraising events and raised nearly $50,000 for research. Better still, they have recruited more than 1,000 potential bone marrow donors through these events. cOnTinUeD »

| aBOVe, lefT |

Lacey horwitch with her mother, Laura | R i G h T | John

cunningham, Md

To learn how you can become a bone marrow donor, visit bethematch.org. For more information or to support Weiss’s or Cunningham’s research, please contact Jennifer Goodnow at jgoodnow@mcdmail.uchicago.edu.

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oPeNiNg iN earLY 2013 The University of Chicago medicine Center for Care and Discovery