Neal Rosen, MD, PhD
New York, New York
Director, Center for Mechanism-Based Therapy
Enid A. Haupt Chair in Medical Oncology
Member, Sloan Kettering Institute Molecular Pharmacology Program
Memorial Sloan Kettering Cancer Center
New York, New York
Developing novel therapeutic combinations to inhibit tumor growth and treat advanced breast and endometrial cancers.
Metastatic breast and endometrial cancers may respond to initial treatment but eventually become resistant to conventional therapies. Abnormal estrogen receptors and a mutated cancer gene, PIK3CA, and the protein it codes phosphatidylinositol kinase-3 (PI3K), generate unregulated signals that drive the growth of many of these tumors. However, inhibitors of estrogen receptors and PI3K have been mostly unsuccessful in clinical trials because cancer cells adapt by activating alternative growth pathways and are able to survive the treatment. Dr. Rosen is working to understand why this is and to develop improved therapies for advanced breast and endometrial cancers.
Dr. Rosen and his team recently discovered why PI3K inhibitors have limited efficacy and have used that information to develop novel strategies to improve patient outcomes. He and his team recently developed a novel drug that selectively inhibits, TORC1, a gene that regulates the PI3K signaling pathway. So far, this has proven to be an effective treatment strategy for endometrial and breast cancers. This year, his team developed a novel drug that significantly reduces the effects of estrogen receptors in breast cancer. They found that when combined with the anti-estrogen drug Fulvestrant, it has remarkable antitumor effects.
Dr. Rosen plans to test the combination of his novel drug and Fulvestrant in patients. He is continuing to work on ways to inhibit estrogen receptors and will test several inhibitors in breast cancer models. Next, Dr. Rosen and his team plan to study resistance to PI3K inhibitors in estrogen receptor-positive, HER2-positive, and triple-negative breast cancer models. Lastly, the team will study the effects of the TORC1 in endometrial and breast cancer models that also have a PI3K mutation.
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.
The Joseph and Arlene Taub Foundation Award
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