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FINDING CURES TOGETHER<sup>SM</sup>

SU2C-Cancer Research UK-Lustgarten Foundation Pancreatic Cancer Dream Team: Reprogramming of Transcriptional Circuitry to Control Pancreatic Cancer

Leader

Daniel D. Von Hoff, MD, FACP

Daniel D. Von Hoff, MD, FACP
Physician-in-Chief and Distinguished Professor, Translational Genomics Research Institute (TGen); Professor of Medicine, Mayo Clinic

Co-leaders

Ronald M. Evans, PhD

Ronald M. Evans, PhD
Professor and Director, Gene Expression Laboratory, Salk Institute for Biological Studies; Howard Hughes Medical Institute Investigator

Gerard I. Evan, PhD

Gerard I. Evan, PhD
Sir William Dunn Professor and Chair, Department of Biochemistry, University of Cambridge

Overview

The Dream Team's 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.

Progress to Date

The SU2C-CRUK-Lustgarten Foundation Pancreatic Cancer Dream Team is deep into its work to "reprogram" the cellular regulatory mechanisms that drive the growth of cancerous tumors. This includes laboratory experiments and clinical trials testing its hypothesis on the role of "superenhancer" regions of the genome.

Amount Of Funding:

$12 million over a three-year period

Principals

Joshua D. Rabinowitz, MD, PhD, Princeton University
David Propper, MD, St. Bartholomew's Hospital

Advocates

E. Howard Young
Suzanne Berenger