Exploiting Metabolic Vulnerabilities to Target Multidrug-Resistant Ovarian Cancer
Abstract
High-grade serous ovarian carcinoma (HGSOC) is the most prevalent histosubtype of epithelial ovarian cancer. Poly(ADP-Ribose) polymerase (PARP) inhibitors have become the standard-of-care for HGSOC patients. How-ever, resistance to PARP inhibitors occurs in homologous-recombination (HR)-proficient disease. Novel combinatorial approaches are now being explored to overcome de novo or acquired resistance. For instance, inhibitors of the DNA damage response protein Ataxia Telangiectasia Mutated (ATM) are now in clinical trials in combination with PARP inhibitors. Unfortunately, our data and others demonstrates a multi-drug resistant subset of HGSOC cells that persist after combined treatment with ATM and PARP inhibitors. Thus, the long-term goal of this proposal is to develop a novel therapeutic strategy to overcome this multi-drug resistant phenotype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1195471
Entities
People
- Katherine M Aird
Organizations
- University of Pittsburgh