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Darren Carpizo, MD, PhD
Associate Professor of Surgery
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey
- Seeking to identify novel anti-cancer drugs.
- Laboratory studies are conducted to test a promising series of new compounds in BRCA and triple negative breast cancer.
- These efforts are creating a new pipeline of novel therapeutics for the treatment of BRCA1 mutant tumors.
Individuals with inherited mutations in the BRCA gene have high risk of developing breast cancer. Most BRCA breast cancers tend to be of the triple negative (TNBC) subtype, an aggressive form of breast cancer for which there are no targeted therapies. Drs. Carpizo and Ganesan have developed a new class of drugs that restore a powerful tumor suppressing protein that is often mutated in TNBC.
Full Research Summary
TP53 is a potent suppressor of tumor growth, but is the most commonly mutated gene in cancers, particularly in basal-like, triple negative (TNBC) and BRCA1-driven cancers. Restoring the anti-cancer function of mutant TP53 with a small molecule drug has long been considered one of the “holy grails” of cancer drug development.
Dr. Carpizo's laboratory identified a new class of anti-cancer drugs called zinc metallochaperones (ZMCs) that targets tumors with mutations in TP53. In the last year, they reported that the ZMC drug they developed is particularly effective in killing breast cancer cells that harbor a BRCA1 mutation.
In the upcoming year, Drs. Carpizo and Ganesan will perform key translational research to accelerate the development of ZMCs to the clinic. They hope to identify a novel ZMC with drug-like properties that shows efficacy in laboratory cancer models.
In addition, they have identified a new series of compounds and a new candidate for the treatment of TNBC and will investigate these in laboratory models.
These studies are paving the way to new, targeted therapies for very aggressive breast cancers.
Darren Carpizo, MD, PhD, is a surgical oncologist specializing in the management of hepato-biliary and pancreatic cancers. Seventy-five percent of his time is devoted to laboratory research in the area of Developmental Therapeutics in both the basic and translational science arenas. Dr. Carpizo’s laboratory recently made a significant contribution to the field of p53 targeted drug development by identifying a lead compound that reactivates mutant p53. He is currently leading a multi-disciplinary group of investigators studying the mechanism of the mutant p53 reactivating drug which including biochemists, structural biologists and medicinal chemists. He is also leading a translational clinical trial to understand the mechanism of action of Hedgehog inhibitors in patients with surgically resectable pancreatic cancer.