title: Evaluation of the methods to identify patients who may benefit from PARP inhibitor use.
abstract: The effectiveness of poly (ADP-ribose) polymerase inhibitors (PARPi) in treating cancers associated with BRCA1/2 mutations hinges upon the concept of synthetic lethality and exemplifies the principles of precision medicine. Currently, most clinical trials are recruiting patients based on pathological subtypes or have included BRCA mutation analysis (germ line and/or somatic) as part of the selection criteria. Mounting evidence, however, suggests that these drugs may also be efficacious in tumors with defects in other genes involved in the homologous recombination repair pathway. Advances in molecular profiling techniques together with increased research efforts have led to a better understanding of the molecular aberrations underlying this BRCA-like phenotype and helped broaden the concept of BRCAness. Hence, it is likely that the list of predictive biomarkers for PARPi therapy will increase in future. There is currently no gold standard method of testing for PARPi response and no universal guidelines are in place on how to incorporate biomarker testing into routine clinical diagnostics. In this review, we explore the concept of BRCAness and highlight the different methods that have been used to identify patients who may benefit from the use of these anticancer agents. The identification of predictive biomarkers is crucial in improving patient selection and expanding the clinical applications of PARPi therapy.
authors.affiliation: Department of PathologyNational University Health System, Singapore, Singapore.
authors.forename: Diana
authors.initials: D
authors.lastname: Lim
authors.affiliation: Lee Kong Chian School of MedicineNanyang Technological University, Singapore, Singapore Cancer Genetics ServiceDivision of Medical Oncology, National Cancer Centre, Singapore, Singapore Joanne.Ngeow.Yuen.Yie@singhealth.com.sg.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ngeow
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics; D015415:Biomarkers; D004249:DNA Damage; D004260:DNA Repair; D015870:Gene Expression; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D015415:Biomarkers; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases
keywords: BRCA; BRCAness; PARP inhibitors; biomarkers; homologous recombination