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FINDING CURES TOGETHER<sup>SM</sup>

SU2C Colorectal Cancer Dream Team: Targeting Genomic, Metabolic and Immunological Vulnerabilities of Colorectal Cancer

Leader

Luis A. Diaz Jr., MD

Luis A. Diaz Jr., MD
Head of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center

Co-leaders

Lewis C. Cantley, PhD

Lewis C. Cantley, PhD
Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian Hospital

Zhenghe John Wang, PhD

Zhenghe John Wang, PhD
Professor of Genetics and Genome Science, School of Medicine, Case Western Reserve University Co-leader, GI Cancer Genetics program (GICG), Case Comprehensive Cancer Center

Charles S. Fuchs, MD, MPH

Charles S. Fuchs, MD, MPH
Director of Yale Cancer Center and Physician-in-chief at Smilow Cancer Hospital

Overview

The Dream Team will focus on three areas of research that have the potential to impact all stages of colorectal cancer. The emphasis of the first two areas of research is on the potential of immunotherapy and targeted therapy to revolutionize the treatment of colorectal cancer, while the last area of study will evaluate strategies to target different colorectal cancer subtypes specifically.

The team will determine the mechanisms of resistance to immunotherapies and targeted therapies, and devise new strategies to overcome the resistance.

Genomic abnormalities can be used to define distinct subgroups of cancer. Two major subgroups of colorectal cancer—those with a mutation in the KRAS/BRAF gene, and those with a mutation in the PIK3CA gene—are susceptible to high dose of vitamin C combined with depletion of a nutrient called glutamine. Drugs developed to target these vulnerabilities were efficient to slow down or cure colorectal cancers of the two subgroups in animal studies. This Team will evaluate if these promising findings can be transposed to patients with similar genomic abnormalities.

Progress to date:

The team's work in correlating genomic features and immune signatures in colorectal cancer has shown that a particular signaling pathway in cancer cells -- the Wnt pathway – can be a driver of resistance to immunotherapy. This suggests that the Wnt pathway is a potential target for treatment that would help immunotherapies to work better in defeating the cancer. The Team has shown the potential of aspirin as a treatment for colorectal cancer that is driven by a certain type of genetic mutation. And finally, the Team's work on cell-free DNA is showing that it can be helpful in detection and treatment of colorectal cancer.

Amount Of Funding:

$12 million

Principals

Ryan B. Corcoran, MD, PhD, Massachusetts General Hospital Cancer Center
Nilofer S. Azad, MD, Johns Hopkins University

Advocates

Anjee Davis
Ivelisse M. Page
Joanna Fuchs, MD
Martha Raymond
Thomas Herbert Marsilje
Vanessa L. Whiting