PARP inhibitors: shifting the paradigm in the treatment of pancreatic cancer

Med Oncol. 2021 Apr 23;38(6):61. doi: 10.1007/s12032-021-01507-9.

Abstract

Pancreatic cancer, being one of the most fatal cancers, is the 7th leading cause of death globally. Cancer that is resistant to current treatment proves that there is a need for personalized and targeted therapy, based on the tumor and genomic markers. Pembrolizumab and Larotrectinib are examples of current medications used as targeted therapy in pancreatic cancer. Pancreatic cancer has many different molecular subgroups, providing the opportunity for the development of new drugs that can target these groups. Poly (ADP-Ribose) polymerase inhibitors (PARPi) are a group of drugs inhibiting PARP to decrease the stability of the cancer cells. Currently, PARPi are mostly used in ovarian and breast cancer. There are multiple studies that have shown positive effects of PARPi in decreasing the tumor burden in advanced pancreatic cancer. PARPi are the future of pancreatic cancer management, and hence it is important to understand their mechanism, resistance pathways, and their application in the real world.

Keywords: Advanced pancreatic cancer; PARP inhibitors; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Biomarkers, Tumor
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Phthalazines / pharmacology
  • Piperazines / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use

Substances

  • Antineoplastic Agents
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • olaparib