Inhibitors of the Fanconi Anaemia pathway as potential antitumour agents for ovarian cancer

Sarah Taylor, Mark Arends, Simon Langdon

Research output: Contribution to journalArticlepeer-review

Abstract

The Fanconi anaemia pathway is an important mechanism for cellular DNA damage repair, which functions to remove toxic DNA interstrand crosslinks. This is particularly relevant in the context of ovarian and other cancers which rely extensively on ICL generating platinum chemotherapy as standard of care treatment. These cancers often respond well to initial treatment, but reoccur with resistant disease and upregulation of DNA damage repair pathways. The Fanconi anaemia pathway is therefore of great interest as a target for therapies that aim to improve the efficacy of platinum chemotherapies, and reverse tumour resistance to these. In this review, we discuss recent advances in understanding the mechanism of ICL repair by the FA pathway, and the potential of the component parts as targets for therapeutic agents. We then focus on the current state of play of inhibitor development, covering both the characterisation of broad spectrum inhibitors and high throughput screening approaches to identify novel small molecule inhibitors. We also consider synthetic lethality between the Fanconi anaemia pathway and other DNA damage repair pathways as a therapeutic approach.
Original languageEnglish
JournalExploration of Targeted Anti-tumour Therapy
Early online date29 Feb 2020
DOIs
Publication statusE-pub ahead of print - 29 Feb 2020

Keywords

  • Fanconi anaemia protein
  • ovarian cancer
  • carboplatin
  • cisplatin
  • inhibitors
  • DNA Repair

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