Aberrations in DNA repair pathways in cancer and therapeutic significances

Akira Motegi, Mitsuko Masutani, Ken ichi Yoshioka, Tadayoshi Bessho

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

Cancer cells show various types of mutations and aberrant expression in genes involved in DNA repair responses. These alterations induce genome instability and promote carcinogenesis steps and cancer progression processes. These defects in DNA repair have also been considered as suitable targets for cancer therapies. A most effective target so far clinically demonstrated is “homologous recombination repair defect”, such as BRCA1/2 mutations, shown to cause synthetic lethality with inhibitors of poly(ADP-ribose) polymerase (PARP), which in turn is involved in DNA repair as well as multiple physiological processes. Different approaches targeting genomic instability, including immune therapy targeting mismatch-repair deficiency, have also recently been demonstrated to be promising strategies. In these DNA repair targeting-strategies, common issues could be how to optimize treatment and suppress/conquer the development of drug resistance. In this article, we review the extending framework of DNA repair response pathways and the potential impact of exploiting those defects on cancer treatments, including chemotherapy, radiation therapy and immune therapy.

Original languageEnglish (US)
Pages (from-to)29-46
Number of pages18
JournalSeminars in Cancer Biology
Volume58
DOIs
StatePublished - Oct 2019

Keywords

  • Homologous recombination repair
  • Mismatch repair
  • Nucleotide excision repair
  • PARP
  • Synthetic lethality

ASJC Scopus subject areas

  • Cancer Research

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