DNA Damage Repair Inhibitors-Combination Therapies

Cancer J. 2021 Nov-Dec;27(6):501-505. doi: 10.1097/PPO.0000000000000561.


DNA damage response and repair (DDR) is responsible for ensuring genomic integrity. It is composed of intricate, complex pathways that detect various DNA insults and then activate pathways to restore DNA fidelity. Mutations in this network are implicated in many malignancies but can also be exploited for cancer therapies. The advent of inhibitors of poly(ADP-ribose) polymerase has led to the investigation of other DDR inhibitors and combinations to address high unmet needs in cancer therapeutics. Specifically, regimens, often in combination with chemotherapy, radiation, or other DDR inhibitors, are being investigated. This review will focus on 4 main DDR pathways-ATR/CHK1, ATM/CHK2, DNA-PKcs, and polymerase θ-and the current state of clinical research and use of the inhibitors of these pathways with other DDR inhibitors.

Trial registration: ClinicalTrials.gov NCT03057145 NCT02723864 NCT03330847 NCT02264678 NCT04065269 NCT04267939 NCT02588105.

Publication types

  • Review

MeSH terms

  • Combined Modality Therapy
  • DNA Damage*
  • DNA Repair / genetics
  • Humans
  • Mutation
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics

Associated data

  • ClinicalTrials.gov/NCT03057145
  • ClinicalTrials.gov/NCT02723864
  • ClinicalTrials.gov/NCT03330847
  • ClinicalTrials.gov/NCT02264678
  • ClinicalTrials.gov/NCT04065269
  • ClinicalTrials.gov/NCT04267939
  • ClinicalTrials.gov/NCT02588105