Neal Rosen, MD, PhD

2009-2010 BCRF Project:
The Joseph and Arlene Taub Foundation Award

The AKT kinase signaling pathway is activated in a majority of human cancers and in most breast cancers. Inhibition of this pathway would be of enormous therapeutic benefit, if tolerated by patients, but, up to now, no drug that directly inhibits AKT and works in models has been available. Dr. Rosen's work is directed at developing inhibitors of this pathway for therapeutic use. His group's previous work showed that the Hsp90 inhibitor 17-AAG turns off this pathway by destroying HER2 and has remarkable activity in breast cancer. However, this drug is likely to be most efficacious in tumors with high levels of HER2.

They have now developed two novel drugs - one that directly inhibits AKT function, and one that turns AKT off by inhibiting Torc kinase. They have shown that non-toxic doses of these compounds inhibit AKT signaling in laboratory models and effectively inhibit the growth of hormone-dependent and triple-negative breast cancers. These findings have led to the ongoing clinical development of these drugs in breast cancer and other tumors in which this pathway is activated. The goal is to pursue the primary clinical development of these drugs in breast cancer, in which the scientists believe the drugs will have significant activity when given alone or in combination with chemotherapy or other inhibitors of signaling pathways.

Bio:
Dr. Rosen is a Member in the Department of Medicine and in the Molecular Pharmacology and Chemistry Program at Memorial Sloan-Kettering Cancer Center, where he serves as Head of Developmental Therapeutics. He is also a Professor of Pharmacology, Cell Biology and Medicine at Cornell University Medical School.

His major interests are the identification and study of key molecular events and growth signaling pathways responsible for the development of human cancer and the use of this information for developing mechanism-based therapeutic strategies. He has played an important role in the development of tyrosine kinase-mediated signaling inhibitors and has pioneered the concept that cancer cells are dependent on cellular machinery for protein folding.

In the course of this work his laboratory has developed inhibitors of the Hsp90 protein chaperone and validated their anticancer activity in animal models and clinical trials. These inhibitors have now shown significant activity in patients with breast cancer, myelogenous leukemia and multiple myeloma. Currently his laboratory work focuses on using pharmacologic and genetic approaches to develop a detailed understanding of feedback and cross-talk among oncogene-activated pathways in order to develop rational combination therapy for refractory breast and lung cancer, melanoma and other tumors. Multiple novel clinical trials based on the work of the Rosen laboratory are being tested at Memorial Sloan-Kettering and other cancer centers in the United States and internationally.

Dr. Rosen received his undergraduate degree in Chemistry from Columbia College and an MD, PhD in Molecular Biology from the Albert Einstein College of Medicine. He completed a residency in Internal Medicine at the Brigham and Women's Hospital and post-doctoral training and a fellowship in Medical Oncology at the National Cancer Institute. He was on the senior staff of the Medicine Branch at the NCI prior to joining the faculty of Memorial Sloan-Kettering Cancer Center.