Presented to

The Harold E. Eisenberg Foundation June 2018

Stewardship Report

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Our Appreciation

Dear Harold E. Eisenberg Foundation Board Members and Friends,

On behalf of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Division of Hematology/Oncology, we thank The Harold E. Eisenberg Foundation for its steadfast commitment to advance gastrointestinal cancer research.

We extend our heartfelt appreciation for your continued support of the Eisenberg Research Scholar Awards, the Harold E. Eisenberg Gastrointestinal Cancer Tissue Bank, the Oncology Research Nurse Coordinator, as well as your generous commitment last year to establish the Harold E. Eisenberg Foundation GI Cancer OncoSET Program at the Lurie Cancer Center. We are working to greatly expand the integration of the Harold E. Eisenberg Foundation GI Cancer OncoSET Program, tissue bank, and research initiatives that will ultimately improve patient care. This effort spans across groups, including the Department of Surgery, the Department of Pathology, and the Division of Hematology/Oncology. The GI OncoSET Program will open new doors and advance the development of personalized cancer treatment options for patients fighting gastrointestinal cancers.

The following report highlights how your impactful philanthropic funds have been used over the last year. Through important support, such as the Harold E. Eisenberg Foundation Scholar Award, we can provide scientists like Ronen Sumagin, PhD, assistant professor of Pathology, with resources and the protected time needed to ask novel research questions and to explore new ideas aimed at discovering cures for gastrointestinal cancers. Science takes time, and as each Eisenberg Research Scholar continues to advance their work beyond their funding year, your return on your investment will grow exponentially.

The Harold E. Eisenberg Foundation has been an invaluable partner in helping us to propel our GI oncology program and our efforts to provide patients with personalized medicine. As always, we remain grateful for all that you do for the Lurie Cancer Center to raise awareness and funds to advance life-saving cancer medicine. We look forward to continuing to update you on our exciting progress over the years ahead.

Sincerely,

Leonidas C. Platanias, MD, PhD Al B. Benson III, MD, FACP, FASCO Jesse, Sara, Andrew, Abigail, Benjamin, and Elizabeth Lurie Professor of Oncology Professor of Medicine Director, Lurie Cancer Center Associate Director, Cooperative Groups

Lurie Cancer Center

3.5Average

number of weeks it takes to complete

genetic sequencing of

a GI cancer tissue sample

Average number of patients seen on a

weekly basis by the GI cancer team

Number of tissue samples stored in the Harold E. Eisenberg

Gastrointestinal Tissue Bank since it was established in 2008

24,00047Number of clinical trials available in 2017 at the Robert H. Lurie Comprehensive Cancer

Center of Northwestern University for patients with GI cancers

Number of departments and/or divisions at Northwestern that interact with patients with GI cancer

19

Facts at a Glance

150

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The Harold E. Eisenberg Foundation Research Scholar Award (2017-2018)An Interview with Ronen Sumagin, PhD

How are you using the funds received from the Harold E. Eisenberg Foundation?The funds received through the Eisenberg Foundation were used to partially support a laboratory technician who helps with experimental procedures, and for purchases of essential reagents used in the study. Our work is aimed at understanding how chronic inflammation and tissue injury, as seen in inflammatory bowel diseases, contribute to increased incidence of colorectal cancer. We assert that understanding the early mechanistic contributions of chronic inflammation to initiating malignancy will provide us with novel approaches to identify pre-malignant lesions that will advance to invasive cancer, as well as help us to devise novel therapeutic approaches to treat such cancers. We anticipate that understanding how tissue injury contributes to cancer can benefit up to one in four cancer patients.

Do you have any results to share, or unique contributions that you would like to mention that resulted from the Research Scholar Award? During the past year, we have made significant advances on the proposed studies. We are excited to report that we have identified several potential molecules that can be used as prognostic biomarkers for inflammation-induced colorectal cancer. We found that the loss of these molecules in colon tissue is associated with genomic instability (increased mutations rate) leading to cancer. We confirmed this in a mouse model of inflammation and cancer, as well as in a small cohort of human patients. We plan to expand this in the future.

Did any of your findings spark any new or novel hypothesis or avenues of study that you might like to follow in the future?These findings prompted us to hypothesize that injury-induced genomic instability and mutations will be the reason for inactivation of tumor suppressor genes, which are important factors contributing to cancer development. Thus, we started an exciting new project and have promising preliminary results, suggesting that during injury immune cells cause specific genetic deletions in one of the key tumor suppressor genes (TP53) to stop its activity, leading to cancer. We now plan to define (map and sequence) these specific deletions in patients with inflammatory bowel diseases and correlate this with patients that have progressed to cancer, with a goal of using them in the future as predictive markers.

Dr. Sumagin’s Appreciation“I would like to thank the Harold E. Eisenberg Foundation for the important philanthropic work they are doing to support gastrointestinal cancer research. As the available federal funding from national institutes is limited and highly competitive, securing funds to execute novel and groundbreaking projects becomes more and more difficult. Personally, being a junior investigator, where my team and I are still developing our research program, obtaining national funding for new ideas with limited preliminary data is even harder. Thus, support from foundations, such as the Harold E. Eisenberg Foundation, is invaluable to developing these ideas to a stage where we can apply for larger grants in the future.” – Ronen Sumagin, PhD

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2016 Harold E. Eisenberg Foundation Research Scholar Guang-Yu Yang, MD, PhD

Outcomes Summary

Guang-Yu Yang, MD, PhD, was named the inaugural Harold E. Eisenberg Scholar in 2016. Using next generation sequencing approach, Dr. Yang and his team have built a large cohort colorectal carcinoma database of more than 300 cases with a comprehensive gene mutation profile on each since the establishment of the database in 2012. Thanks to support from The Harold E. Eisenberg Foundation, they were able to grow the database from 200 to 300 cases. Within this cohort, Dr. Yang’s group has identified 59 cases of BRAF-mutant colorectal cancer (82% from the right colon). Mutation hotspot analysis showed that the vast majority (93.3%) have the most common V600E BRAF mutation, but next generation sequencing also has identified related mutations in other key cancer-related genes. Dr. Yang is continuing to evaluate the efficacy of two drugs—vemurafenib and decitabine—using a mouse model created from patient-derived BRAF-mutant colon cancer (called a xenograft model or PDX mice). He is also working on developing other 4 Braf and p53 mutant PDX mouse models of colorectal cancer that can be used to study colon cancer and other therapeutic agents. The study on these models will be significant and will enable him to apply for an R01 grant through the National Institutes of Health.

The Harold E. Eisenberg Gastrointestinal Cancer Tissue Bank

The tissue bank at Northwestern, established by The Harold E. Eisenberg Foundation in 2008, continues to be a valuable resource for our scientists, and has enabled them to further their investigations through earned National Institutes of Health grants. The bank currently stores nearly 24,000 colorectal cancer tissue samples (2,000 more from last year) from nearly 1,200 patients, equipping researchers with the ability to study what characterizes cancer tissues and to develop investigations aimed at improving prevention, detection, and treatment.

Clinical Research Nurse – Victoria Maurer, MSN, RN, OCN, CNE

The Harold E. Eisenberg Foundation’s philanthropy supports our clinical research associate within Gastrointestinal Oncology, Victoria Maurer. Victoria coordinates all ongoing clinical trials and helps patients access trials in a number of ways. She reviews the records of all new gastrointestinal oncology patients to determine if they are eligible for a clinical trial. If they are eligible, Victoria presents this option to them along with the attending physician. She also assesses patients who are currently progressing on treatment for trial eligibility. If we do not have an appropriate trial, Victoria reaches out to other centers to help find appropriate trials.

Clinical trials are important for patients with gastrointestinal cancers in order to develop new effective treatments. There are only a limited number of Food and Drug Administration-approved therapies, and as patients are living longer, clinical trials allow us to test new therapeutic options.

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Patient Event: Conversations about Colorectal Cancer

The Lurie Cancer Center’s annual Conversations about Colorectal Cancer program was held on Saturday, September 23, 2017. Colorectal cancer patients and their families were invited to network with other patients while learning about new treatments, clinical trials, and survivorship at this important patient event. Program chair Mary Mulcahy, MD, professor of Medicine in the Division of Hematology/Oncology and clinical practice director at the Lurie Cancer Center, spoke about colorectal cancer and new treatments. We are thankful to The Harold E. Eisenberg Foundation for generously sponsoring this educational event.

Thank You for Your Generosity

Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center ofNorthwestern University are deeply grateful for your continued support. The Harold E. Eisenberg Foundation is accelerating gastrointestinal cancer research now and into the future, bringing us closer to personalized medicine by offering truly customizable treatment solutions and improving care and outcomes for patients with cancer.

If you would like more information regarding this report or the Lurie Cancer Center, please contact:

Elizabeth Gordon Associate Director, Major Gifts Development and Alumni Relations Northwestern University Feinberg School of Medicine Arthur J. Rubloff Building, 9th Floor 420 East Superior Street Chicago, Illinois 60611 P. 312-503-0759E. elizabeth.gordon@northwestern.edu

Impact Report June 2018