Testing for Homologous Recombination Repair or Homologous Recombination Deficiency for Poly (ADP-ribose) Polymerase Inhibitors: A Current Perspective
Poly (ADP-ribose) polymerase inhibitors (PARPis) have demonstrated clinical activity in patients with BRCA1 and/or BRCA2 mutated breast, ovarian, prostate, and pancreatic cancers. Notably, BRCA mutations are associated with defects in the homologous recombination repair (HRR) pathway. This homologous recombination deficiency (HRD) phenotype can also be observed as genomic instability in tumour cells. Accordingly, PARPi sensitivity has been observed in various tumours with HRD, independent of BRCA mutations. Currently, four PARPis are approved by regulatory agencies for the treatment of cancer across multiple tumour types. Most indications are specific to tumours with a confirmed BRCA mutation, mutations in other HRR-related genes, HRD evidenced by genomic instability, or evidence of platinum sensitivity. Regulatory agencies have also approved companion and complementary diagnostics to facilitate patient selection for each PARPi indication. This review aims to summarise the biological basis, clinical validation, and clinical relevance of the available diagnostic methods and assays to assess HRD.
Herzog, Thomas J; Vergote, Ignace; Gomella, Leonard G; Milenkova, Tsveta; French, Tim; Tonikian, Raffi; Poehlein, Christian; and Hussain, Maha, "Testing for Homologous Recombination Repair or Homologous Recombination Deficiency for Poly (ADP-ribose) Polymerase Inhibitors: A Current Perspective" (2023). Department of Urology Faculty Papers. Paper 72.
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This article is the author’s final published version in European journal of cancer (Oxford, England : 1990), Volume 179, January 2023, Pages 136 - 146.
The published version is available at https://doi.org/10.1016/j.ejca.2022.10.021. Copyright © 2022 Merck Sharp & Dohme LLC., a subsidiary Merck & Co., Inc., The Author(s). Published by Elsevier Ltd.. All rights reserved.