May 15, 2006
Center offers new model for developing targeted therapies
Left to right: Ronald DePinho, Kenneth Anderson, Lynda Chin and James DeCaprio lead the Science Discovery Program of the Center for Applied Cancer Science.
In one of the most far-reaching initiatives of Dana-Farber's Strategic Plan, cancer researchers at Dana-Farber and Harvard have built a fully coordinated drug-development center able to convert basic science discoveries into new treatments to reach patients in the clinic.
The Center for Applied Cancer Science (CACS), directed by Dana-Farber's Ronald DePinho, MD, is fully operational, providing scientists across the full range of cancer research with a system for discovering and developing the next generation of targeted therapies. A "center without walls," the CACS is a collection of researchers, technicians, and laboratory and clinical facilities dedicated to discovering those genes needed to form and maintain tumors and translating those discoveries into effective drug treatments.
This systematic approach is meant to bring direction and coherence to a drug-development process that is too often fragmented and haphazard, DePinho remarks. It will provide not only a speedier pathway for the creation and introduction of new drugs, but also dramatically improve the chances that compounds identified as potential drugs are successful in patients.
"Nationwide, only about 11 percent of potential cancer drugs ultimately come to market," DePinho says. "In fully half of those cases, the failure occurs late in the clinical trial process when the drugs prove ineffective against patients' disease. We clearly have to do better."
The solution is to build a system that uses the most advanced science and most thorough testing to carry forward only those therapies with the greatest chance of working. That approach requires a fuller understanding of the array of cancer genes, a clearer picture of how tumor cells interact with the rest of the body, better animal models of human cancers, and rigorous testing each step of the way to ensure both that suspected cancer genes actually do play a role in the disease and that novel agents can block them. It also requires a closer partnership with the pharmaceutical industry, which is uniquely able to develop promising agents into usable therapies.
"The traditional system is too compartmentalized," DePinho asserts. "We need an integrated effort that combines discovery science, and its rich feature of producing unanticipated results, and applied, directed activities that drive the translation of laboratory findings into actual drugs."
Three-part harmony
The Center for Applied Cancer Science, built with the help of philanthropic contributions, consists of three interlocking components:
- A Science Discovery Program, which focuses on the basic biology of various cancer types. The aim is not merely to identify genes that may be involved in cancer, but to understand how those genes function in the context of fully formed tumors. Investigators will focus on the role that other genetic mutations, cell type, and tumor stage play in gene function. Such information will give a fuller picture of the genes' role in tumor maintenance, and of their potential as targets for therapy.
- A Pipeline Program, "a backbone of directed activity," DePinho says, in which investigators seasoned by industry experience drive the process of converting laboratory discoveries into new cancer therapies. This effort will involve screening "monoclonal antibodies" – uniform proteins of the immune system capable of blocking gene targets – as the basis of new therapies, and testing them in tumor tissue samples and mouse models of human cancers.
- A Business Development Program, which will manage drug-development projects and forge ties with industry for drugs that can be tested in clinical trials, while protecting the intellectual property rights of Dana-Farber/Harvard investigators.
The Science Discovery Program will initially concentrate on four types of cancer that are among the most difficult to treat: pancreatic ductal adenocarcinoma, glioblastoma (a brain cancer), multiple myeloma (a blood cancer) and melanoma (which originates in skin cells).
Joining DePinho in the CACS' discovery program leadership are Dana-Farber's Kenneth Anderson, MD, director of the Jerome Lipper Multiple Myeloma Center, who heads up the center's experimental therapeutics work; Lynda Chin, MD, who oversees cancer genomics and genetics; and James DeCaprio, MD, who has responsibility for monoclonal antibody development. Leading the Pipeline Program are Dana-Farber's Alexei Protopopov, PhD, Laura Corral, PhD, Yonghong Xiao, PhD, and Irina Agoulnik, PhD.
Best of both worlds
The simultaneously explorational and goal-oriented nature of the CACS reflects a weaving together of the best of academia and principles of industry, Anderson observes. "At Dana-Farber and Harvard, we have an unrivaled breadth of expertise and technology for studying cancer, detecting cancer genes and designing molecules to block them. By tying each step of the drug-development process into a continuum, we have an extraordinary opportunity to go from fundamental, basic genetic studies all the way up to prototype novel treatments."
And by teaming with industry at certain stages of that process, the CACS becomes even more valuable, Chin comments. "Academia celebrates the individual; industry celebrates the team. In academia, we're good at discovering genes and their mechanism of action, and at running clinical trials. Drug development is where industry shines. Working together, we can make a profound difference in the efficiency of progress against cancer."
"The CACS is an integral component of the research arm of the Institute's Strategic Plan," adds the Institute's Chief Scientific Officer, Barrett Rollins, MD, PhD. "Through its interactions with other Strategic Plan centers as well as individual investigators, we expect the center to help accelerate the pace at which discoveries are turned into meaningful and effective cancer treatments."
- Robert Levy
robert_levy@dfci.harvard.edu
