SU2C Scientific Research Teams
SU2C-CRUK-Lustgarten Foundation Pancreatic Cancer Dream Team: Reprogramming of Transcriptional Circuitry to Control Pancreatic Cancer
Daniel D. Von Hoff, MD, FACP
Physician-in-Chief and Distinguished Professor, TGen; Professor of Medicine, Mayo Clinic
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Ronald M. Evans, PhD
Professor, Director, Gene Expression Laboratory, Salk Institute for Biological Studies; Howard Hughes Medical Institute Investigator
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Gerard I. Evan, PhD
Sir William Dunn Professor, Chain of the Department of Biochemistry, University of Cambridge
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“We are going after pancreatic cancer in a different way. We will use new and existing agents to reprogram the master regulatory biological machinery in cancer cells that drives tumor growth. This machinery comprises molecular complexes of DNA and proteins that are known as ‘super enhancers’ for their ability to coordinate the expression of a large number of genes.” — Daniel D. Von Hoff, MD
Pancreatic cancer is a particularly deadly disease, with a five-year survival rate at less than seven percent. Taking the lives of approximately 40,000 people per year in the U.S. and 8,000 in the U.K., cancer of the pancreas is the 5th leading cause of cancer death worldwide. The disease is typically diagnosed at a late stage and surgery is not an option for the majority of patients. Sadly, even the most recent treatments extend survival in many advanced pancreatic cancer patients by only a few months. New approaches to treatment of pancreatic cancer are desperately needed to help patients survive this terrible disease.
The SU2C-Cancer Research UK-Lustgarten Foundation Pancreatic Cancer Dream Team brings together renowned experts from the U.S. and the U.K. to tackle this problem. Their approach is rooted in the central idea that pancreatic cancers are in essence “wounds” that never heal. Research from members of this Dream Team, and others in the field, have uncovered gene networks in tumors that are similar to those in injured tissues where repair and regenerative mechanisms are essential to restoration of normal function. Unlike the normal system of wound healing that has a shut-off mechanism, in tumors the process remains on, “hijacked” to constantly drive growth. The Dream Team believes that the biological machinery involved is controlled through hot spots in a cell’s DNA called Super Enhancers (SE), which control not only the cancer cell, but also surrounding non-cancerous cells, upon which the cancer cells rely for support. The Dream Team aims to develop new approaches to reset malfunctioning SEs in pancreatic tumors thereby dialing-up the sensitivity to chemotherapy and to anti-cancer immune cells and pushing pancreatic tumors into lasting remission.
To achieve their goals, the Dream Team will take a three-pronged approach. First, they will use cutting-edge technology to identify pancreatic tumor SE hot-spots so that they can understand the biological “hacking” of normal wound-healing regenerative processes. Second, they will seek to understand how SEs allow cancer cells to obtain nutrients from nearby normal cells, while at the same time avoiding detection by the immune system. Third, they will initiate clinical trials in pancreatic cancer with a new class of SE-targeted drugs that are geared to enhance chemotherapy and revitalize the immune response. The trials are slated to start in the first year of the Dream Team’s funding.
Through their efforts, the Dream Team hopes to improve survival of pancreatic cancer patients, at least doubling the one-year survival in advanced pancreatic cancer from 35% to more than 70%, and to maintain remission in patients who have responded to treatment, extending and enhancing the lives of people suffering with this terrible disease.
Meet the SU2C-CRUK-Lustgarten Foundation Pancreatic Cancer Dream Team: