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Opinion: PARP inhibitors in cancer-what do we still need to know?

Andrew J Wicks1,2, Dragomir B Krastev1,2, Stephen J Pettitt1,2

  • 1The CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.

Open Biology
|July 27, 2022
PubMed

Insights

Poly (ADP-ribose) polymerase inhibitors (PARPi) show promise against cancers with DNA repair defects. This review covers PARPi mechanisms, resistance, and improving patient selection and treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective against cancers with homologous recombination DNA repair pathway defects.
  • Understanding PARPi mechanisms and the emergence of drug resistance is crucial for optimizing cancer therapy.

Purpose of the Study:

  • To outline the current consensus on PARPi mechanisms and resistance.
  • To discuss the need for improved companion biomarkers for patient stratification, early resistance detection, and toxicity prediction.
  • To explore potential strategies for treating PARPi resistance.

Main Methods:

  • Literature review and expert consensus synthesis.
  • Analysis of current clinical practices and research findings on PARPi.
  • Discussion of emerging biomarkers and therapeutic approaches.

Main Results:

  • PARPi efficacy is linked to specific DNA repair deficiencies.
  • Drug resistance to PARPi can arise through various mechanisms.
  • Current biomarkers may not fully capture patient response or predict resistance.
  • New strategies are being developed to overcome PARPi resistance.

Conclusions:

  • Refining companion biomarkers is essential for enhancing PARPi therapy effectiveness.
  • Early detection and management of PARPi resistance are critical.
  • Further research into overcoming resistance mechanisms will expand PARPi utility.
Keywords:
PARP inhibitorsbiomarkerscancerdrug resistancesynthetic lethality

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