ADP ribose polymerase inhibitors for treating non-small cell lung cancer: new additions to the pharmacotherapeutic armamentarium

Expert Opin Pharmacother. 2020 Apr;21(6):679-686. doi: 10.1080/14656566.2020.1724283. Epub 2020 Feb 19.

Abstract

Introduction: Poly (ADP-ribose) polymerase inhibitors (PARPi) are already part of the armamentarium of drugs available against ovarian and breast cancer. There is less data available on the efficacy of these drugs in the treatment of non-small cell lung cancer (NSCLC).

Areas covered: The authors have analyzed the preclinical studies that justified the use of PARPi in NSCLC. They then evaluate the in vivo efficacy of the combination of these drugs with chemotherapy, radiotherapy, and immunotherapy.

Expert opinion: Data from clinical trials available to date have discouraged the use of PARPi in association with chemotherapy or radiotherapy in NSCLC. The knowledge available to date opens the door to the use of PARPi in association with immunotherapy. In fact, the activity of these drugs would not be based only on direct cytotoxic action, but also on the modification of the intra-tumor microenvironment, in particular by increasing the expression of PD-L1 on tumor cells. This action might potentially enhance available treatments with a modest increase in toxicity.

Keywords: PARPi; immunotherapy; iniparib; lung cancer; olaparib; rucaparib; veliparib.

Publication types

  • Review

MeSH terms

  • Adenosine Diphosphate Ribose / antagonists & inhibitors*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Chemoradiotherapy
  • Female
  • Humans
  • Immunotherapy
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors / administration & dosage
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Tumor Microenvironment / drug effects

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Adenosine Diphosphate Ribose