The Phoenix-based Translational Genomics Research Institute (TGen) will lead an international Stand Up To Cancer (SU2C) Dream Team of top cancer researchers in a $12 million effort to double the survival of patients with pancreatic cancer, the fourth leading cause of cancer death in the U.S.
Dr. Daniel D. Von Hoff — TGen Physician-in-Chief and Distinguished Professor, Chief Scientific Officer at HonorHealth Research Institute, and Professor of Medicine at Mayo Clinic — will lead the Dream Team, which includes nearly two dozen researchers in the U.S. and United Kingdom.
“Our overarching aim is to develop therapies that greatly improve a person’s survival,” Dr. Von Hoff said. “In this project, we will pursue pancreatic cancer in a different way than ever before. We will focus on reprogramming the master machinery in cancer cells that drive tumor growth. Our targets are the complexes of DNA and proteins known as ‘super enhancers’ for their ability to affect a large number of genes.”
“We are learning more and more about the complexities of pancreatic cancer,” said Erkut Borazanci, M.D., M.S., clinical investigator and principal investigator at the HonorHealth Research Institute, the only clinical trials site in Arizona. “Thanks to this award by SU2C we will be able to offer novel therapies for patients with pancreatic cancer.”
This is TGen’s third SU2C Dream Team, the second focusing on pancreatic cancer. A third Dream Team led by TGen is investigating new treatments for melanoma.
The new international SU2C Pancreatic Cancer Dream Team was announced today during the 2015 International Conference on Molecular Targets and Cancer Therapeutics in Boston, sponsored by the American Association for Cancer Research (AACR), the National Cancer Institute, and the European Organisation for Research and Treatment of Cancer. The AACR is SU2C’s scientific partner and will administer the grant.
Cancer Research U.K. and The Lustgarten Foundation joined SU2C in selecting the team, following a rigorous process, and providing $12 million in research funding over three years.
Co-leaders of the new Pancreatic Cancer Dream Team are: Ronald M. Evans, Ph.D., Professor and Director of the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, Calif.; and Gerard I. Evan, Ph.D., Professor and Chair of the Department of Biochemistry at the University of Cambridge, U.K.
Serving as principal investigators on the team are Christopher Heeschen, M.D., Ph.D., lead, Centre for Stem Cells in Cancer & Ageing at the Barts Cancer Institute, Queen Mary University of London, U.K.; David Propper, M.D., a consultant medical oncologist at Barts Cancer Institute and the London NHS Trust; and Joshua D. Rabinowitz, M.D., Ph.D., professor of chemistry and integrative genomics at Princeton University.
Other institutions participating in the project are: St. Bartholomew’s Hospital, University of Pennsylvania, and Moores Cancer Center at UC San Diego Health. Mayo Clinic in Arizona will also contribute to the research.
The team also includes two advocates: Suzanne Berenger of England and Howard Young of the U.S., both of whom are pancreatic cancer survivors. Young, an Atlanta businessman and a Board Member of the TGen Foundation, credits TGen and Dr. Von Hoff with saving his life.
The new Dream Team’s research will focus on reprogramming the biology of cells in pancreatic tumors — both the cancer cells themselves as well as the surrounding non-cancerous cells upon which the cancer cells rely for support — so that the tumors can be stopped.
They have found biological pathways in pancreatic tumors controlled by areas in the DNA called “super enhancers” (SEs) that are similar to those in injured tissues where repair and regenerative mechanisms are essential to restore 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. Another way to look at it is the normal wound-healing process is hacked to produce the cancer.
Pancreatic cancer has a dismal outlook, with a five-year survival rate of less than 10 percent, the worst of any cancer. Each year, it takes the lives of more than 40,000 Americans.
“As devastating as these statistics are, they don’t begin to describe the considerable pain and suffering associated with this disease,” said Dr. Von Hoff. “Our team brings together the very best experts on both sides of the Atlantic, and we feel confident that we will soon bring better treatments to the patients that need our help today.”
A major part of the study will be taking drugs that target super enhancers, as well as combinations of SE drugs with chemotherapies and immunotherapeutic drugs, into clinical trials within the first year of the study. Clinical trials are planned in the U.K., Pennsylvania, San Diego, and at HonorHealth in Scottsdale.
“Cancer is a like a wound that does not heal,” Dr. Von Hoff said. “We think the control of healing happens through super enhancers, and in cancer that control mechanism is malfunctioning. We hope to reboot the super enhancers and send the pancreatic cancer into durable remission.”
In 2009, TGen was selected to lead one of the first SU2C Dream Teams. It also was supervised by Dr. Von Hoff and also focused research on pancreatic cancer. That work resulted in a treatment regimen that has produced some long-term survivors of this disease.
In 2011, TGen was named to lead a SU2C Dream Team, in association with the Melanoma Research Alliance, aimed at addressing unmet needs of melanoma patients. A nationwide set of clinical trials stemming from this project’s research began earlier this year.
A Joint Scientific Advisory Committee (JSAC) — composed of highly accomplished researchers and physician-scientists and advocates — conducted a rapid, interactive and rigorous evaluation of the applications and recommended the Dream Team announced today.
“Cancer of the pancreas poses some very difficult challenges because the diagnosis is often made at a late stage, and surgery is often impossible,” said Phillip A. Sharp, Ph.D., Nobel laureate, institute professor at the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, and chairperson of the JSAC. “The Dream Team will bring new insights such as inhibition of novel gene control processes to the battle against this terrible disease.”
Serving as vice-chairs of the JSAC were: Richard M. Marais, Ph.D., director of the Cancer Research UK Manchester Institute, where he also heads the Molecular Oncology Group; and David A. Tuveson, M.D., Ph.D., director of research for The Lustgarten Foundation and director of The Lustgarten Foundation Pancreatic Cancer Research Lab at Cold Spring Harbor Laboratory.
Cancer Research UK, the largest charitable funder of cancer research in the world, supports a broad range of research to better understand, diagnose, prevent and treat all cancers. The international collaboration between SU2C and Cancer Research UK launched with a live SU2C telecast on Channel 4 in the United Kingdom in 2012. Through annual telecasts on Channel 4, the U.K. SU2C campaign has generated more than $35 million to accelerate groundbreaking cancer research in the U.K. and abroad. The new Dream Team is the first supported by the transatlantic collaboration between SU2C and Cancer Research UK.
Dr. Iain Foulkes, Cancer Research UK’s executive director of research funding, said: “Survival from pancreatic cancer is low. Frankly, progress has not been good enough and it’s why we have invested $6 million in this Dream Team. These are among the finest researchers in the world and we’re really excited by the potential of their ideas in the fight against this terrible disease.”
The Lustgarten Foundation, located in Bethpage, N.Y., is America’s largest nonprofit private funder of pancreatic cancer research dedicated to scientific and medical advancements related to the prevention, diagnosis, treatment, and cure of pancreatic cancer. As a longstanding partner of SU2C, The Lustgarten Foundation’s co-funding of this new Dream Team will be the third Dream Team supported by the Foundation.
“To eradicate pancreatic cancer will take a collaborative effort, and private funding plays a critical role in accelerating the development of new clinical trials for this deadly disease,” said Kerri Kaplan, executive director and chief operating officer of The Lustgarten Foundation. “This international collaboration will bring together leading global experts in the field of pancreatic cancer research, and together, we will focus on developing new therapies and innovative approaches so patients can benefit and live longer lives.”
As the official scientific partner of SU2C since its launch in 2008, the AACR provides scientific leadership, expert peer review, and grants administration for SU2C’s extensive research program.