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BCRF Grantee Since

2003

Donor Recognition

The Joseph and Arlene Taub Foundation Award

Area(s) of Focus

Neal Rosen, MD, PhD

Director, Center for Mechanism-Based Cancer Therapies
Enid A. Haupt Chair in Medical Oncology
Member, Medicine & Molec Pharm & Chemistry
Director, Center for Mechanism-Based Cancer Therapeutics
Memorial Sloan Kettering Cancer Center
New York, New York

Current Research

Cancer growth is fueled by dysregulated signaling pathways caused by mutated or defective proteins that regulate the pathway. In a way, tumor cells become “addicted” to the growth-promoting benefits of the aberrant signaling that results. For this reason, targeted therapies have been developed in hopes of preventing tumor growth by blocking the activity of the mutated protein in the pathway. This approach, however, has not resulted in substantial clinical benefit in clinical trials. Research by Dr. Rosen and colleagues has shown that while inhibition of these oncogenic pathways with targeted drugs slows tumor growth, it also results in the activation of parallel signaling pathways, reducing the anti-tumor effect of the drug. The focus of Dr. Rosen’s BCRF research is in understanding tumor response to pathway inhibition and to develop combination treatments to improve response to these targeted therapies. In the coming year, he and his team will concentrate on a combination approach to inhibit a signaling pathway called PI3K that is over-activated in most breast cancers. The goal of the current project is to determine the most effective combinations and then test these ideas in clinical trials.

Bio

Neal Rosen, MD, PhD, is the Director of the Center for Mechanism-Based Therapeutics at Memorial Sloan Kettering Cancer Center and a Member in the Program in Molecular Pharmacology and Chemistry. His major interests include the study of the key molecular events and growth signaling pathways responsible for human cancers, and the use of this information for developing effective therapies. Dr. Rosen has played a leading role in the development of inhibitors of tyrosine kinase and RAS-mediated signaling and has pioneered the concept that feedback reactivation of parallel signaling pathways is a common cause of adaptive resistance to selective pathway inhibitors. Recent work includes the elucidation of the biochemical and biologic mechanisms of action of RAF inhibitors, the mechanisms underlying resistance to these compounds, and studies on the role of ERK-dependent feedback in tumors with RAF or RAS mutation. This research has led to many international clinical trials with promising early results.