PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

Cancer Res Commun. 2024 Nov 1;4(11):2976-2985. doi: 10.1158/2767-9764.CRC-24-0339.

Abstract

Olaparib, a PARP inhibitor, is effective against various cancers, including prostate cancer. However, resistance to olaparib poses a significant challenge. This study uncovers that mitochondrial alterations and PINK1 gene overexpression contribute to this resistance in prostate cancer cells. Enhanced mitochondrial functionality and increased PINK1 expression in olaparib-resistant cells underscore the importance of targeting mitochondrial dynamics and PINK1 to develop more effective treatments for overcoming olaparib resistance in prostate cancer.

MeSH terms

  • Cell Line, Tumor
  • Drug Resistance, Neoplasm* / genetics
  • Humans
  • Male
  • Mitochondria* / drug effects
  • Mitochondria* / metabolism
  • Phthalazines* / pharmacology
  • Phthalazines* / therapeutic use
  • Piperazines* / pharmacology
  • Piperazines* / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Protein Kinases* / genetics
  • Protein Kinases* / metabolism

Substances

  • olaparib
  • Phthalazines
  • Piperazines
  • PTEN-induced putative kinase
  • Protein Kinases
  • Poly(ADP-ribose) Polymerase Inhibitors