The University of Toledo Health Science Campus Division was awarded a 5-year, $524,419 Project Grant under the National Cancer Institute's (NCI) Cancer Treatment Research Program (CFDA 93.395) to investigate the molecular mechanisms by which fatty acid synthase (FASN) contributes to PARP inhibitor (PARPi) resistance in triple-negative breast cancer (TNBC). The research aims to:
Determine how proton pump inhibitors (PPIs) inhibit FASN activity,
Elucidate how FASN regulates PARP1 and BRCA1 expression to drive PARPi resistance, and
Evaluate the synergistic effects of combining PPIs with PARPi in BRCA-proficient and -deficient TNBC cells.
The successful completion of this study is expected to establish FASN overexpression as a mechanism of PARPi resistance and provide the scientific basis to evaluate the combination of PPIs and PARPi as a novel treatment approach for TNBC patients, regardless of BRCA status.