The Stand Up 2 Cancer Colorectal Dream Team

As part of our coverage of the American Association for Cancer Research annual meeting, held April 14 –18 in Chicago, Ill., we spoke with Luis Diaz, MD, a medical oncologist who heads the division of solid tumor oncology at the Memorial Sloan Kettering Cancer Center in New York City. Dr. Diaz's research team  is developing novel ways to use cancer genetics for better diagnosis and treatment, and he specializes in the treatment of patients with colon and pancreatic cancers. Dr. Diaz, along with colleagues from five other institutions, was awarded $12 million in 2017 to focus on colorectal cancer research and treatment as part of the Stand Up 2 Cancer Colorectal Dream Team. He discussed the progress of the project so far, which aims to dissect the genomic, metabolic, and immunologic vulnerabilities of colorectal cancer.   

-Interviewed by Anna Azvolinsky

Cancer Network: First, tell us about the Stand Up 2 Cancer Colorectal Dream Team. What are the overall goals of the project and who are your colleagues on this team?

Dr. Diaz: The Stand Up 2 Cancer Colorectal Dream Team is a proposal that was awarded to us here at Memorial Sloan Kettering, our colleagues at Cornell, Case Western, Massachusetts General Hospital, Yale Cancer Center, Dana Farber, and Johns Hopkins. [These institutions] comprise the Dream Team. There are five [goals]. The first is to study how to harness the immune system to attack colorectal cancer. The second is to harness the molecular genetics of colon cancer. The third is targeting certain metabolomics of colorectal cancer, and the final one is precision prevention, which is to use the tools we’ve learned in [furthering] the other four [goals] to try to prevent colorectal cancer at the earliest stages.

Cancer Network: What do we know about the genomic landscape of colorectal cancer, and what are you learning or [do you] hope to learn through this Stand Up 2 Cancer effort?

Dr. Diaz: What we are trying to do is to find not only new biological mechanisms, but also new therapies that might have a positive impact on the outcome of patients-and new insights that might even go beyond colorectal cancer and have a global impact on different kinds of cancers. The thing we are most excited about is that we might be able to use some of these tools for the early detection and prevention of colon cancer.

Cancer Network: So what, specifically, are the tools that you think could be used for early detection and prevention?

Dr. Diaz: Basically, [we’re asking the question], could we use any of the molecular genetic tools to identify patients who are at high risk and utilize therapeutic tools to treat patients who are high risk.  So we prevent these high-risk scenarios from actually turning into real-life cancer.

Cancer Network: And as far as the metabolic and immunologic characteristics of colon cancer [are concerned]? Can you tell us about the progress of the project on this front?

Dr. Diaz: We define the mismatch repair colorectal cancers as being highly responsive to immunotherapy. The question is, can we detect cancer at the earliest possible stages, or in those patients at high-risk for mismatch repair–deficient tumors and actually treat those people with immunotherapy even before they develop cancer?

Cancer Network: Have there been any trials started or that will start soon, based on any of these molecular and immunological vulnerabilities you and your colleagues discovered through this project?

Dr. Diaz: Yes. The studies that we have are looking at things like tumor mutational burden and microsatellite instability across tumor types in very early stages-and for colon cancer, even at the polyp stage before there is even cancer at all. We can apply these tools at these early stages. To give you a specific example, there is a trial with an anti-PD1 [programmed death 1] checkpoint inhibitor antibody in patients with an exceptionally high mutational burden.