At the Forefront of Cancer Care and Discovery®

Spring 2016 | cancer.uchicago.edu

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Reaching for the Moon:An Historic Effort to Fight CancerIt was the spring of 1991, and at the age of

48, a successful biomedical engineer was diagnosed with glioblastoma multiforme,

the most aggressive type of brain cancer, after having a seizure in his doctor’s office. Surgery was not an option because of the location of the tumor, and symptoms caused by the cancer ruled out radiation therapy. At the time, the odds were grim, as the five-year survival was less than 5 percent. He died two weeks later. In the 25 years since, there have been some significant advancements in the treat-ment of this deadly cancer, including the introduction of the chemotherapy temo-zolamide with concurrent radiotherapy. Nevertheless, the median survival is still only 15 months. Glioblastoma multiforme and other types of the deadliest cancers have not seen robust improvements in survival despite revolutionary advancements in personalized medicine and impressive declines in overall cancer mortality in recent years. No one understands the limited progress made with some of these cancers better than Vice President Joe Biden, who lost his oldest son, Beau, to brain cancer at the age of 46 last summer. Therefore, it should come as no surprise that President Barack Obama charged Biden with leading the Administration’s National Cancer Moonshot initiative, first announced in Obama’s State of the Union address in January. This moonshot is ambitious. Its major goals are to accelerate cancer research efforts aimed at developing new ways to prevent, diagnose and treat cancer, reducing barri-ers to enhance data access, and facilitating collaborations among all stakeholders – researchers, physicians, patients, advocates, non-profit organizations, and industry part-ners. Importantly, the initiative proposes to invest $1 billion to accomplish these objec-tives, including focused efforts in cancer prevention, early detection, immunotherapy and combination therapy, tumor and micro-environment genomic analysis, pediatric cancer, and data sharing/bioinformatics. The moonshot has stirred a national dialogue around cancer research and care that arguably has not been seen since the

But, what really lies at the heart of this initiative are the patients and their loved ones. We will continue to fight for new and better treatments so our patients can see new and better days. And,

this effort can only be bolstered by the renewed support and interest in cancer research generated by the moonshot initiative. The Comprehensive Cancer Center is proud to be a part of such

an important and groundbreaking time in our history. And, in this issue of Pathways to Discovery, we highlight the ways in which we are working toward a cure each day. Also in this issue, we share some of the career achievements of our faculty, along with recent research breakthroughs generated in our labs and clinics. Finally, we feature some of the outreach and philan-thropy efforts that are an integral part of our continued efforts.

It is an exciting time in cancer research, and we thank you for joining us on this journey.

Regards,

Michelle M. Le Beau, PhDDirector, The University of Chicago Medicine Comprehensive Cancer Center; Arthur and Marian Edelstein Professor of Medicine

In his 2015 State of the Union address, President Obama asked Vice President Biden to lead a “moonshot” effort to cure cancer. At the University of Chicago Medicine Comprehensive Cancer Center, we have been making strides toward this lofty goal each year. From innovative clinical trials to the latest immunotherapies, our researchers and clinicians are at the forefront of discovery.

FROM THE DIRECTOR

Michelle M. Le Beau, PhD

“War on Cancer” was declared by President Richard Nixon in 1971. “The fact this is now getting attention at highest levels of government really creates a sense of excitement,” said Walter Stadler, MD, Fred C. Buffett Professor of Medicine and Surgery and deputy director of the Comprehensive Cancer Center. What does the initiative mean to the University of Chicago Medicine Compre-hensive Cancer Center, and the patients and communities the Comprehensive Cancer Center serves? “I think it’s a great possibility that Chicago will be the place where a number of cures for cancer are developed,” said Michelle Le Beau, PhD, Arthur and Marian Edelstein Professor of Medicine and director of the Comprehensive Cancer Center. The Comprehensive Cancer Center is

well positioned to lead the way in many aspects of the initiative. For example, investigators in our Immunology and Cancer scientific program are international leaders in basic cancer immunology research, clinical studies applying immunotherapy to a wide range of cancer types, and overcoming resistance to immunotherapy. The University of Chicago has an exciting partnership with the National Cancer Institute to build and house the nation’s most comprehensive cloud-based database, called the Genomic Data Commons, an extraordinary resource of cancer genomic profiling data that will be accessible to the entire cancer research community. An additional strength of the Comprehensive Cancer Center is understanding and addressing the causes, including biological, environmental,

lifestyle and socioeconomic factors, which contribute to the development of cancer in our community and, in particular, to the unequal burden of cancer faced by underrepresented populations. The moonshot will drive progress in all phases of the cancer care continuum – from prevention through treatment and survivorship – for all patients. For patients and families touched by those cancers that have not seen the needle move much in the last several decades, the moonshot initiative provides hope that future generations will view any cancer diagnosis as something they live with, rather than die from. We thank the Administration for making this a national priority, and look forward to Vice President Biden blazing the trail with us.

How is the Comprehensive Cancer Center Already Tackling the Cancer Moonshot Initiative?

Pathways to Discovery

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Pathways to Discovery is a quarterly publication of The University of Chicago Medicine Comprehensive Cancer Center.Spring 2016, Volume 10, Number 4

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Open Cancer Clinical Trials Patient enrollment is underway for more than 350 clinical trials at the University of Chicago Medicine Comprehensive Cancer Center. A few of our newly launched clinical trials include: n An Open-Label, Phase I/II, Dose

Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Patients with Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin’s Lymphoma and in Com-bination with Endocrine Therapy in Patients with Locally Advanced or Metastatic Hormone Receptor-Posi-tive Breast Cancer

n A Randomized, Multi-center Phase III Study of Nivolumab versus Sorafenib as First-Line Treatment in Patients with Advanced Hepatocellular Car-cinoma

n A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MOXR0916 and MPDL3280A in Patients with Locally Advanced or Metastatic Solid Tumors

n A Multi-Center Open-Label Study of the Bruton’s Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination with MEDI4736, in Subjects with Relapsed or Refractory Lymphomas

n A Phase II Study of Pembrolizumab (MK-3475) as Monotherapy in Subjects with Previously Treated Unresectable Locally Advanced or Metastatic (Stage IV) Microsatellite Instability-High Colorectal Adenocarcinoma

To learn more about these or any other Comprehensive Cancer Center clinical trial, call toll-free 1-855-702-8222 for adult clinical trials or 1-773-702-6808 for pediatric clinical trials, or go to cancer.uchicago.edu and click on Search Clinical Trials in the blue box.

RESEARCH HIGHLIGHTSIdentification of genetic variant in pediatric B-cell precursor acute lymphoblastic leukemiaPediatric B-cell precursor acute lympho-blastic leukemia (BCP-ALL) is the most common childhood cancer and is characterized by the presence of too many immature B cells in the blood and bone marrow and recurring acquired chromo-somal abnormalities. There is accumulating evidence from experimental models and genome-wide association studies (GWAS) that there may be inherited genetic or epigenetic susceptibility factors that impact disease onset and progression. Kenan Onel, MD, PhD, associate professor of pediatrics, led an international group of scientists from the University of Chicago, Vanderbilt University, St. Jude Children’s Research Hospital, University of California San Francisco, Australia, France and Germany to discover additional pediatric BCP-ALL variants. They analyzed four pediatric ALL GWAS datasets, comprising more than 2,100 cases and 5,500 controls of European ancestry, and identified and replicated a specific location on chromosome band 9p21.3 associated with susceptibility to BCP-ALL. Assess-ing function of this gene variant, they found that was it correlated with reduced expression of CDKN2B which encodes a cell-cycle regulator and known tumor suppressor. Furthermore, they found that a previously identified variant in this gene locus was associated with controlling the expression of CDKN2A, another cell cycle tumor suppressor. These findings suggest that common inherited genetic variation at 9p21.3 is associated with increased risk for BCP-ALL and sheds light on the potential molecular mechanism responsible. (Hungate et al., Nat Commun 7:10635, 2016)This work was supported by grants from the Na-tional Institutes of Health (HD0433871, CA129045, CA40046,MH101820, U01CA176063 and U01GM92666), the St Baldrick’s Foundation, the American Cancer Society, and the Cancer Research Foundation. The Children’s Oncol-ogy Group (COG) GWAS was also supported by grants from the National Institutes of Health (U10 CA98543 and U24 CA114766). The French GWAS was performed by the CNG (Centre National de Génotypage) and the CEPH. The ESCALE study was supported by grants from INSERM, the Fondation de France, the Association pour la Recherche sur le Cancer, ANSES, Cent pour sang la vie, INCa, ANR, and the Cancéropôle Ile de France. The German GWAS was sup-ported by the German Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN), the popgen biobank, the Federal Radiation Protec-tion Agency (3609S30013), the Deutsche Krebshilfe and the Madeleine Schickedanz Kinderkrebs-Stiftung. Dr. Onel is a member of the Hematopoiesis and Hematological Malignan-cies scientific program.

Breast cancer risk is increased in childhood cancer survivorsWith the remarkable improvements in survival rates for childhood cancer over the last several decades, over 80% of children currently diagnosed with cancer before the age of 21 will be cured. Unfortunately, childhood cancer survivors face a higher risk of premature death, the leading cause of which is second cancers. Evidence indicates that female survivors exposed to chest radiation are at a much higher risk for breast cancer later in life, but it was unclear whether women not exposed to radiotherapy were also at an increased risk. In a multi-institutional study led by Tara Henderson, MD, associate professor of pediatrics, using the large Childhood Cancer Survivor Study cohort of childhood cancer survivors treated at 26 centers in North America, breast cancer risk in women never exposed to chest radiotherapy was evaluated. The investigators found that these women had a four-fold increased risk to develop breast cancer at a young age when compared to the general population, and the risk was highest among sarcoma and leukemia survivors. Additionally, expo-sure to specific classes of chemotherapy, including alkylators and anthracyclines, were associated with an increased breast cancer risk. This work identifies risk factors beyond chest radiotherapy for childhood cancer survivors to develop breast cancer and suggests that these women may benefit from early breast cancer surveillance to improve long-term outcomes. (Henderson et al., J Clin Oncol December 23 Epub ahead of print, 2015)This study was supported by grants from the National Can-cer Institute (U24CA55727, K07CA134935, R01CA136783 [C.S.M.], K05CA160724, and R01CA134722) and the Meg Berté Owen Foundation. Dr. Henderson is a member of the Cancer Prevention and Control scientific program.

PROCLAIM trial evaluates new treatment regimen for advanced lung cancerNon-small-cell lung cancer represents the vast majority of all lung cancers, and many cases present at an advanced stage in which the cancer has spread locally, making it inoperable, but has not spread to distant sites. For these patients, standard care is typically a combination of chemotherapeu-tic agents with radiotherapy, although the precise optimal drug and radiation regimen has not been clearly established.

The large, randomized, multicenter phase III PROCLAIM trial, involving 125 institutions in 21 countries, sought to identify a more effective, less toxic chemoradiotherapy treatment regimen for patients with advanced non-small-cell lung cancer. The study, led by Everett Vokes, MD, John E. Ultmann Professor of Medicine and Radiation Oncology, specifi-cally investigated whether an antifolate drug called pemetrexed in combination with the chemotherapeutic agent cisplatin, alongside concurrent radiation therapy and followed by additional pemetrexed therapy, would be more effective than the standard treatment of a different chemo-therapy combination (etoposide-cisplatin) with radiation. The pemetrexed-cisplatin combination had been used successfully in other settings, and other studies had suggested it might reduce the risk of distant metastases. Although the pemetrexed-cisplatin combination was found to be safe and well tolerated by patients in this trial, this combination was not superior to the standard of care in terms of improving overall survival of advanced non-small-cell lung cancer patients. This work is impor-tant because it indicates that concurrent chemoradiation remains the standard of care for treatment of stage III non-small-cell lung cancer patients, and there is more work to do to find better treatment combinations. (Senan et al., J Clin Oncol Jan 25 Epub ahead of print, 2016)Dr. Vokes is a member of the Pharmacogenomics and Ex-perimental Therapeutics scientific program.

Adolescent and young adult blood cancer patients experience psychological traumaAlthough hematological malignancies only account for about 8 percent of all new

cancer cases in the U.S. each year, they account for about 20 percent of cases in the adolescent and young adult (AYA) popula-tion aged 15-39. As AYA patients often face intense and lengthy treatment regimens and are at a vulnerable age, they are met with unique psychosocial challenges often underestimated by their health care providers. A research team led by Christopher Daugherty, MD, professor of medicine, and involving Jennifer McNeer, MD, assis-tant professor of pediatrics, and Wendy Stock, MD, Anjuli Seth Nayak Professor in Leukemia, studied the distress faced by AYA patients with acute myeloid leukemia, acute lymphoblastic leukemia or lymphoma who were undergoing treatment or were in remission within two years of therapy completion. The investigators found that more than one quarter of all participants met the criteria for depression, 23 percent met for the criteria for anxiety, and 13 percent met the criteria for posttraumatic stress. Additionally, surveying health care providers revealed a significant level of inaccuracy and inconsistency in provider perception of mental health status in these patients. This work highlights the need to consider and evaluate the psychological effects of cancer, encourage dialogue between physicians and patients, and provide the necessary support for young cancer patients. (Muffly et al., Cancer Jan 7 Epub ahead of print, 2016).This study was funded by a Conquer Cancer Foundation Young Investigator Award to Lori Muffly, MD. Dr. Daugh-erty is a member of the Cancer Prevention and Control scientific program, and Drs. McNeer and Stock are members of the Hematopoiesis and Hematological Malignancies scientific program.

We are pleased to present our 2015 Annual Report!n http://cancer.uchicago.edu/AnnualReport2015/Within these pages you’ll find examples of how we’re answering cancer’s most challenging ques-tions through innovative research and individualized treatments. Thank you for all your support, and we look forward to seeing what 2016 brings. #AnswerCancer

2015 Comprehensive Cancer Center Annual Report

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At the Forefront of Cancer Care and Discovery®

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MEMBER NEWS

1 David Meltzer, MD, PhD, professor of medicine, is among 18 faculty mem-bers who recently received named or distinguished professorships. Meltzer was awarded the title of Fanny L. Pritzker Professor of Medicine, Economics and Public Policy.

2 Gini Fleming, MD, professor of medicine, is this year’s recipient of the Society of Gynecologic Oncology’s Harry Long Multidisciplinary Award, to recognize her outstanding contributions to the field of gynecologic cancers through leadership, mentorship, and

scholarly collaborations. Dr. Fleming also received the distinction of Fellow of the American Society of Clinical Oncology (FASCO).

3 Philip Hoffman, MD, professor of medicine, was awarded the 2016 American Society of Clinical Oncology (ASCO) Excellence in Teaching Award, which recognizes an ASCO member who has inspired and shaped trainees’ practice of cancer medicine.

4 Olufunmilayo I. Olopade, MBBS, Walter L. Palmer Distinguished Service Professor of Medicine and Human

Genetics, and associate dean for global health, was awarded the Franklin D. Roosevelt Four Freedoms Medal on September 29 in New York City. The award recognizes Olopade’s path-finding research in Nigeria and America showing that women of African heritage can be genetically susceptible to more aggressive, earlier onset forms of breast cancer.

5 Karen Kim, MD, professor of medicine, is the recipient of a 2016 Impact Award from the Chicago Foundation for Women. The Impact Awards celebrate Chicago-

area women and men for their dedication to increasing resources and opportunities for women and girls in the Chicago area.

6 Susan Cohn, MD, professor of pediatrics, was awarded the 2016 American Society of Clinical Oncology (ASCO) Pediatric Oncology Award. This award recognizes Cohn’s outstanding career and her scientific achievements in neuroblastoma. Dr. Cohn also received the distinction of Fellow of the American Society of Clinical Oncology (FASCO).

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Comprehensive Cancer Center faculty and staff participated in November’s Movember Founda-tion movement to raise awareness about men’s health. Their “Monsters of the Mo” team raised more than $6,800 to support research.

Pictured (left to right) Diane West, PhD, Geoffrey Greene, PhD, Russell Szmulewitz, MD, Donald Vander Griend, PhD, Walter Stadler, MD, Kathleen Goss, PhD, and Suzanne Conzen, MD

Leading U.S. Cancer Centers Urge HPV Vaccination for Prevention of CancerThe University of Chicago Medicine Comprehensive Cancer Center has joined with the National Cancer Institute (NCI) and dozens of other NCI-designated cancer centers across the U.S. to call attention to low rates of human papilloma virus (HPV) vaccination. This is a serious public health threat—and a missed opportunity. HPV vaccination is an effective, but tragically underused method for preventing many cases of cancer including cervical cancer. As national leaders in cancer research and clinical care, we urge parents and health care providers to protect the health of our children. Read more on the Science Life blog: http://sciencelife.uchospitals.edu/2016/01/27/leading-us-cancer-centers-urge-hpv-vaccination-for-the-prevention-of-cancer/

University of Chicago Researchers Present at American Society of Hematology (ASH) Annual MeetingComprehensive Cancer Center researchers made a big contribution to the year’s premier scientific meeting on blood cancers, also called hema-tological – or heme – malignancies. The conference drew more than 25,000 attendees from around the world to discuss the latest biological discoveries, clinical trials and personalized therapies for leukemia, lymphoma and multiple myeloma. Read more on the Science Life blog: http://sciencelife.uchospitals.edu/2015/12/15/leaders-in-blood-cancer-research-and-care-share-latest-advances-at-ash-annual-meeting/

Movember for Men’s Health

Pathways to Discovery

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IN THIS ISSUE…

1 Reaching for the Moon: An Historic Effort to Fight Cancer

Spring 2016cancer.uchicago.edu

4 UChicago Medicine Patient’s Personal Journey Inspires Bowie Benefit at Metro Chicago

4 Auxiliary Board Hosts ‘All in for the Cure’ Fundraiser for Cancer Research

2 2015 Comprehensive Cancer Center Annual Report

Support cancer research through the UCCRF:donatetocancer.uchicago.edu

Pathways to

At the Forefront of Cancer Care and Discovery®

The University of Chicago Cancer Research Foundation held its annual gala “All in for a Cure” on March 12, 2016 at the Michigan Shores Club in Wilmette. 180 attendees enjoyed dinner, dancing, live and silent auctions, and a lively Vegas casino. The Auxiliary Board is dedicated to raising funds to aid in the prevention and cure of cancer, and at this event, they raised over $200,000. Funds raised will support the work of clinical scientists Mark Applebaum, MD, clinical instructor of pediatrics, Megan McNerney, MD, PhD, assistant professor of pathology, and Blase Polite, MD, associate professor of medicine. The emcee was TV personality and author Jennifer Weigel and auctioneer was Karen Sorbo.

ALL IN FOR A CURE

WO M E N ’S B OAR D

50th Annual Grand AuctionSaturday, November 12, 2016 The Four Seasons Hotel Chicago, IL50

UChicago Medicine Patient’s Personal Journey Inspires Bowie Benefit at Metro ChicagoA survivor of throat cancer, Metro owner Joe Shanahan was treated at the University of Chicago Medicine, which he credits with providing exceptional care and support. Upon hearing of David Bowie’s death and reflecting on his own experience with cancer, Shanahan approached Sons of the Silent Age and eagerly suggested they partner with the University of Chicago to raise money. For him the concert, which took place on March 4, was a way to pay tribute to both Bowie and the doctors who saved his life. Read more on Give to Medicine: https://givetomedicine.uchicago.edu/donor-stories/music-man’s-personal-journey-inspires-bowie-benefit

SAVE THE DATE! The UCCRF Women’s Board will celebrate 50 years of the Grand Auction on November 12, 2016. The gala is the most prestigious and longest running auction event in Chicago history. The Board has raised over $17 million for cancer research, which has enabled researchers to leverage additional grant funding of over $45 million. To learn more visit: cancerboard.org

From left to right: Beth Aldrich, Beth Mercola, Lydia DeLeo, Dr. Michelle M. Le Beau, Lisa Hoffman, Laurie Lawlor