Role of akt activation in PARP inhibitor resistance in cancer

Ferenc Gallyas, Balazs Sumegi, Csaba Szabo

Research output: Contribution to journalReview article

Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors have recently been introduced in the therapy of several types of cancers not responding to conventional treatments. However, de novo and acquired PARP inhibitor resistance is a significant limiting factor in the clinical therapy, and the underlying mechanisms are not fully understood. Activity of the cytoprotective phosphatidylinositol-3 kinase (PI3K)-Akt pathway is often increased in human cancer that could result from mutation, expressional change, or amplification of upstream growth-related factor signaling elements or elements of the Akt pathway itself. However, PARP-inhibitor-induced activation of the cytoprotective PI3K-Akt pathway is overlooked, although it likely contributes to the development of PARP inhibitor resistance. Here, we briefly summarize the biological role of the PI3K-Akt pathway. Next, we overview the significance of the PARP-Akt interplay in shock, inflammation, cardiac and cerebral reperfusion, and cancer. We also discuss a recently discovered molecular mechanism that explains how PARP inhibition induces Akt activation and may account for apoptosis resistance and mitochondrial protection in oxidative stress and in cancer.

Original languageEnglish
Article number532
JournalCancers
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 2020

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Keywords

  • Apoptosis resistance
  • Cytoprotection
  • MTOR
  • Mitochondrial protection
  • Oxidative stress
  • PARP-Akt interplay
  • PI3K

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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