In an effort to improve the success rate of investigational cancer drugs entering clinical trials, the Center for Applied Cancer Science (CACS) of the Dana-Farber Cancer Institute and Merck and Co., Inc., have established a collaboration to identify promising drug targets, and develop therapeutic candidates to reach those targets.

"Currently, there is a 95 percent failure rate in cancer drug development," says Ronald DePinho, MD, of the CACS. "Drugs that pass safety testing in Phase I trials too often fail to show efficacy in later-stage trials, or prove effective in only a small subset of patients."

The use of genomic information in identifying therapeutic targets and appropriate trial designs requires the integration of genomics with function, mechanism and, importantly, cancer biology, explains Dana-Farber's Lynda Chin, MD, who will be the senior investigator in the CACS-Merck alliance. "By actively facilitating communication," says Chin, "this new agreement represents an important advance toward true team science between Dana-Farber and one of world's the leading pharmaceutical companies."

Under the terms of the agreement, Merck will provide up-front and research support funding to the CACS as well as milestone and royalty payments upon market approval. The CACS will investigate drug targets using integrative and cross-species genomic analysis and stringent multi-level functional and clinicopathological validation testing. The CACS will work together with Merck to shepherd the drug assay development of lead compound discovery and then work together to test these drugs in CACS's highly sophisticated model systems that closely replicate human disease.

The collaboration will also involve CACS faculty, under the direction of James DeCaprio, MD, and Kenneth Anderson, MD, working together with scientists from Merck Research Laboratories, to further evaluate tumor pathobiology and clinical outcomes to better pinpoint the tumor types most susceptible to the drug.

Dana-Farber established the CACS, which is supported by the Robert A. and Renée E. Belfer Foundation, in 2004. CACS is part of the Robert A. and Renée E. Belfer Institute for Innovative Cancer Science, which also houses the Arthur and Rochelle Belfer Center for Cancer Genomics.

The CACS consists of team scientists and core laboratory facilities for identifying genetic alterations in cancer, pinpointing those alterations most crucial to tumor formation and maintenance, validating those targets in a wide range of cell and tissue cultures assays and sophisticated animal models, and, in the case of monoclonal antibodies, developing them into useful therapies. The CACS retains the right to develop its antibodies independent of the Merck collaboration.

"Collaborations with external partners are an integral and essential part of our oncology research and development strategy," says Stephen Friend MD., PhD, senior vice president and franchise head, Oncology, Merck Research Laboratories. "Through this collaboration with Dana-Farber, one of the world's premier cancer centers, we hope to establish an open and collaborative relationship through our common goal of advancing cancer treatment."

Merck, established in 1891, is a global leader in the discovery, development, manufacture, and marketing of vaccines and medicines. Its products include treatments for conditions ranging from diabetes and osteoporosis, to HIV infection and asthma.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.