In October, the MMRF, the world's largest private funder of myeloma-specific research, proudly announced that a team of researchers from the Dana-Farber Cancer Institute is the recipient of its 2004 Collaborative Program Grant. The grant, which provides $1.5 million over a 3-year period, is designed to foster unique collaborations among researchers and institutions to help bring new therapies to the clinic quickly.

The Collaborative Program, titled Development of Molecularly-Based Combination Therapy for Multiple Myeloma, is led by Kenneth C. Anderson, MD, Kraft Family Professor of Medicine and the Director of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute. According to Dr. Anderson, the program consists of three closely-linked core projects that are centered on the common theme that the interaction between the myeloma cell and its microenvironment is important for tumor cell growth and survival, as well as the development of resistance to therapy.

• Project 1 will use genomics to identify optimal combinations of novel agents and is led by principal investigators Ruben Carrasco, MD, PhD, Li Cheng, PhD, and Nikhil C. Munshi, MD. Agents to be evaluated include those that target the myeloma cell and its bone marrow microenvironment, drugs that target myeloma cells at the cell surface, and drugs that target the bone marrow microenvironment.


• Combinations of novel agents identified in Project 1 will be evaluated in Project 2 for their impact on signaling mediating myeloma cell growth, survival, drug resistance, and apoptosis in the lab (see figure). Project 2 is led by Dr. Anderson, Dharminder Chauhan, PhD, and Teru Hideshima, MD, PhD.


• Project 3 will confirm the efficacy of these combined therapies against human myeloma cells in mouse models of human myeloma. This project is led by Constantine Mitsiades, MD, PhD and Edie Toolen, PhD. The in vivo effects of combined therapies in Project 3 will also be correlated with in vitro data from Projects 1 and 2 to validate the scientific rationale for combining single agents.

Collectively, these studies will provide the preclinical basis for designing Phase I collaborative clinical trials evaluating combinations of novel agents. "The grant offers an unprecedented opportunity to rationally combine active single novel agents to enhance cytotoxicity on one hand and overcome drug resistance on the other," notes Dr. Anderson. "We are now poised to investigate this strategy-which has helped cure childhood acute lymphocytic leukemia and adult testicular cancer-in myeloma."