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BCRF Grantee Since


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 & Molecular Pharmacology & 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 to understand tumor response to pathway inhibition and to develop combination treatments to improve response to these targeted therapies. In the past year, they have elucidated key aspects of the mechanism of action of a class of drugs called PI3K inhibitors. They showed that they worked better when given intermittently rather than daily and developed a novel inhibitor of mTOR, a protein that works with PI3K, that is significantly more effective than current mTOR inhibitors. They now plan to compare the effectiveness of PI3K inhibitors and that of the new mTOR inhibitor in models of the different breast cancer subtypes. They will determine the mechanisms by which the tumor cell adapts to these drugs and use this information to develop new strategies for combination therapies and optimal scheduling of drug delivery. The goal of this project is to determine the most effective combinations and protocols and then test these ideas in clinical trials.


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.