Testing for homologous recombination repair or homologous recombination deficiency for poly (ADP-ribose) polymerase inhibitors: A current perspective

Thomas J. Herzog*, Ignace Vergote, Leonard G. Gomella, Tsveta Milenkova, Tim French, Raffi Tonikian, Christian Poehlein, Maha Hussain

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)136-146
Number of pages11
JournalEuropean Journal of Cancer
Volume179
DOIs
StatePublished - Jan 2023

Funding

This work was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. , Rahway, NJ, USA , and AstraZeneca LTD, Cambridge, UK , which are codeveloping olaparib. The funders participated in study design, data analysis and interpretation, and article writing. All authors had full access to the data and had final responsibility for the decision to submit the article for publication. Medical writing and/or editorial assistance was provided by Lei Bai, PhD, Max Chang, PhD, Holly C. Cappelli, PhD, CMPP, and Christina Vitolo of ApotheCom (Yardley, PA ) and was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. , Rahway, NJ, USA , and AstraZeneca LTD, Cambridge, UK , which are codeveloping olaparib.

Keywords

  • Breast neoplasms
  • Homologous recombination
  • Metastatic pancreatic neoplasms
  • Ovarian neoplasms
  • Poly(ADP-ribose) polymerase inhibitors
  • Prostate neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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