OncoTargets and Therapy (Feb 2022)
PARP Inhibitor Applicability: Detailed Assays for Homologous Recombination Repair Pathway Components
Abstract
Geraldine O’Sullivan Coyne,1 Chris Karlovich,2 Deborah Wilsker,3 Andrea Regier Voth,3 Ralph E Parchment,3 Alice P Chen,1 James H Doroshow4 1Early Clinical Trials Development Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; 2Leidos Biomedical Research Inc, Molecular Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA; 3Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA; 4Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USACorrespondence: James H Doroshow, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Room 3A44, Bethesda, MD, 20892, USA, Tel +1 240 781-3320, Fax +1 240 541-4515, Email [email protected]: Poly(ADP-ribose) polymerase inhibitors (PARPi) have been in clinical use since 2014 for certain patients with germline BRCA1/2 mutations, but as evidence and approvals for their use in a wider range of patients grow, the question of how best to identify patients who would benefit from PARPi becomes ever more complex. Here, we discuss the development and current state of approved selection testing for PARPi therapy and the ongoing efforts to define a broader range of homologous recombination repair deficiencies that are susceptible to PARP inhibition.Keywords: next-generation sequencing, genomic scar, mutational signature, Rad51, BRCAness
