Journal article

Role of akt activation in PARP inhibitor resistance in cancer

  • Gallyas, Ferenc Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary - Szentagothai Research Centre, University of Pcs, 7624 Pecs, Hungary - HAS-UP Nuclear-Mitochondrial Interactions Research Group, 1245 Budapest, Hungary
  • Sumegi, Balazs Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary - Szentagothai Research Centre, University of Pcs, 7624 Pecs, Hungary - HAS-UP Nuclear-Mitochondrial Interactions Research Group, 1245 Budapest, Hungary
  • Szabo, Csaba Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary - Chair of Pharmacology, Department of Medicine, University of Fribourg, 1700 Fribourg, Switzerland
    01.03.2020
Published in:
  • Cancers. - 2020, vol. 12, no. 3, p. 532
English 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
Faculty
Faculté des sciences et de médecine
Department
Médecine 3ème année
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/308743
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