reviewMolecular CancerJun 20, 2020GOLD OA

PARP inhibitor resistance: the underlying mechanisms and clinical implications

Central South University · Hunan Cancer Hospital · +1 more institution

PubMed
Indexed incrossrefdoajpubmed

Abstract

Due to the DNA repair defect, BRCA1/2 deficient tumor cells are more sensitive to PARP inhibitors (PARPi) through the mechanism of synthetic lethality. At present, several PAPRi targeting poly (ADP-ribose) polymerase (PARP) have been approved for ovarian cancer and breast cancer indications. However, PARPi resistance is ubiquitous in clinic. More than 40% BRCA1/2-deficient patients fail to respond to PARPi. In addition, lots of patients acquire PARPi resistance with prolonged oral administration of PARPi. Homologous recombination repair deficient (HRD), as an essential prerequisite of synthetic lethality, plays a vital role in killing tumor cells. Therefore, Homologous recombination repair restoration (HRR)…

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531
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Authors

6

Topics & keywords

Keywords
  • Synthetic lethality
  • DNA repair
  • PARP inhibitor
  • Poly ADP ribose polymerase
  • Biology
  • Homologous recombination
  • Cancer research
  • DNA damage
UN Sustainable Development Goals
  • Good health and well-being
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