Alvaro Monteiro, Ph.D.
H. Lee Moffitt Cancer Center & Research Institute
Tampa, FL, United States
Project: Tackling PARP inhibitor resistance through functional proteomics
Research Areas: Chemotherapy Resistance
Summary:
There has been significant progress in ovarian cancer treatment especially with the development and approval of PARP inhibitor drugs. Despite this progress, a sizable percentage of patients do not respond or stop responding to PARP inhibitor treatment. Dr. Monteiro proposes to apply a novel approach to understand resistance to PARP inhibitors that may either be present from the start or develop during treatment. Dr. Montiero and colleagues believe that tumors with defects in BRCA1 or BRCA2 that do not respond to PARP inhibitors will show significant changes in both protein complexes that interact with the PARP inhibitor drug and in other modifications on proteins. They will look for these changes both in ovarian cancer cells and in frozen tissues from tumors to identify markers of PARP inhibitor resistance and to identify new targets for rational combination therapies that can overcome resistance. If successful, the results of this project may extend the benefits of PARP inhibitor therapy to a significantly larger segment of ovarian cancer patients, identify patients who would not benefit from PARP inhibitors so that alternative therapies can be explored earlier, and find potential targets for combination therapy to reverse or bypass PARP inhibitor resistance.