June 16, 2009
'Dream team' scientists focus on rogue pathway in women's cancers
Thomas Roberts, PhD, and Jean Zhao, PhD, both of Cancer Biology, are two members of the Stand Up 2 Cancer "dream team" that includes Dana-Farber scientists.
Last September, a celebrity-studded telethon, Stand Up 2 Cancer (SU2C), broadcast on the three major networks raised more than $100 million to accelerate the flow of cancer treatments from the lab to the bedside. Now, a "dream team" that includes multiple Dana-Farber researchers has been chosen by SU2C to receive a substantial fraction of the funds raised.
The Dana-Farber scientists are key members of one of the five multi-institutional "dream teams" announced May 27 that will share $73.6 million over three years. The team that represents Dana-Farber and six other institutions was awarded $15 million to test drugs that treat breast, ovarian, and endometrial cancers by blocking a source of overactive cell-growth signals.
SU2C is the charitable initiative of the Entertainment Industry Foundation, whose goal is to take promising ideas for improved cancer treatments emerging from laboratories, and translate them rapidly into drugs and other modalities that can benefit patients immediately.
Thomas Roberts, PhD, of Cancer Biology, is Dana-Farber's leader on the dream team, which also includes scientists from Beth Israel-Deaconess Medical Center (BIDMC), Memorial Sloan-Kettering Cancer Center, M.D. Anderson Cancer Center, Herbert Irving Comprehensive Cancer Center, Vanderbilt-Ingram Cancer Center, and Vall d'Hebron Oncology Research Institute.
The team's focus is a cellular signaling network known as PI3-Kinase (PI3K) that has been found to be abnormally active in a large proportion of women's cancers. Blocking the overactive PI3K network has shown promise in animal studies and has begun testing in patients, using drugs called PI3K inhibitors.
"At Dana-Farber, we have a very strong clinical research contingent, and trials are about to start with the first PI3K inhibitors," says Roberts. "In pre-clinical work, we are working with the drugs to see what they do in animals and how to best optimize their use in combinations with other drugs. And we are seeing how resistance to the inhibitors arises in this pathway, so we can stay one jump ahead."
The overall leader of the dream team is Lewis Cantley, PhD, of BIDMC, who co-discovered the P13K molecular network along with Roberts. A handful of PI3K inhibitors are currently undergoing testing in patients, but thus far it has been impossible to predict which patients are likely to benefit from which drugs: a major goal of the project is to better match patients with particular drugs. This form of "personalized medicine" is designed not only to benefit individual patients, but to accelerate development of lifesaving therapies.
"Increasingly we understand that one size doesn't fit all when it comes to cancer. We need to devise individualized treatments for groups of patients," says Eric Winer, MD. He is the clinical trials leader for the entire PI3K dream team.
"In this project we have planned clinical trials for using several of the PI3K inhibitors, alone and in combination with other targeted therapies," Winer adds. "We are trying to understand in whom they are effective, and, when they stop working, what causes the resistance to the drugs."
Other Dana-Farber scientists on the team include J. Dirk Iglehart, MD, director of the Women's Cancers Program (WCP); Andrea Richardson, MD, PhD, director of the WCP tissue bank at Dana-Farber; David Livingston, MD, director of the Program in Human Genetics; Ursula Matulonis, MD, director of the Program in Medical Gynecologic Oncology at Dana-Farber; Ian Krop, MD, PhD, of the Breast Oncology Center; Jean Zhao, PhD, of Cancer Biology, and Joyce Liu, MD, of Gynecologic Oncology.
The SU2C dream team structure encourages scientists to reach across institutional boundaries and to share data freely. So far, Roberts says, this approach is succeeding, aided by meetings, e-mails, phone calls, and videoconferencing.
"It has been very impressive how well this is working," he says.
— Richard Saltus
Richard_Saltus@dfci.harvard.edu
