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Neal Rosen, MD, PhD
Director, Center for Mechanism-Based Therapy
Enid A. Haupt Chair in Medical Oncology
Member, Sloan Kettering Institute Molecular Pharmacology Program
Member, Memorial Sloan Kettering Cancer Center
New York, New York
Goal: To improve targeted therapy for breast and endometrial cancer.
Impact: Dr. Rosen is developing combination therapies that inhibit growth signals that allow breast and endometrial tumors to progress. If shown to be effective, these treatments could improve outcomes for those with advanced metastatic breast and endometrial cancers.
What’s next: Dr. Rosen will continue to improve combination therapies and target other pathways to treat breast and uterine cancers.
While there are therapies available to treat endometrial and metastatic breast cancer (MBC)—breast cancer that has spread to other tissues—these cancers will progress, even if they initially respond to treatment. Dr. Rosen is focused on the protein PI3K, which activates a pathway that drives the growth of many MBC and endometrial cancers. He and his team have recently developed two new drugs that, when combined in laboratory studies, target these pathways and kill tumor cells.
Full Research Summary
Research area: Improving outcomes in patients with aggressive cancers with new targeted strategies.
Impact: Patients with advanced metastatic breast and endometrial cancers may initially respond to treatment but their tumors eventually progress. It has been shown that the growth of many of these tumors is driven by the mutated cancer gene, PI3 kinase (PI3K). Drugs targeting PI3K have had limited success in clinical trials because the cancer cells adapt by activating alternative growth pathways and resist the treatment. Dr. Rosen and his team developed a combination of drugs that effectively kills cancer cells in laboratory models. These studies may provide new options for patients with advanced breast or endometrial cancer.
Current investigation: Dr. Rosen is conducting laboratory studies to exploring alternative strategies to target the growth-promoting pathways that drive aggressive cancers.
What he’s learned so far: Dr. Rosen’s team developed a combination therapy that has been approved to treat advanced hormone-dependent breast cancer. They have also identified a promising new inhibitor of a protein called TORC1 and expect the drug to enter phase I clinical trials in 2020.
What’s next: Dr. Rosen and his team plan to improve PI3K and TORC1 targeted therapies and apply what they have learned to other pathways that regulate tumor response to therapy in breast and uterine cancer.
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.
BCRF Investigator Since
The Joseph and Arlene Taub Foundation Award