Review Article Open Access
Volume 1 | Issue 4 | DOI: https://doi.org/10.33696/Signaling.1.021

NOXA the BCL-2 Family Member behind the Scenes in Cancer Treatment

  • 1Université de Nantes, Inserm, CRCINA, F-44000 Nantes, France
  • 2SIRIC ILIAD, Nantes, Angers, France
  • 3Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA
  • 4Institut de Cancérologie de l’Ouest, 15 Rue André Boquel, 49055 Angers, France
+ Affiliations - Affiliations

Corresponding Author

Sophie Barillé-Nion, sophie.barille@univ-nantes.fr

Received Date: July 07, 2020

Accepted Date: September 17, 2020


NOXA is a critical mediator of stress responses to anticancer drugs. This BH3-only protein sets the apoptotic threshold in cancer cells in response to chemotherapies by counteracting the prosurvival BCL-2 family protein MCL-1. A complex and dynamic network relying on both highly controlled gene transcription activity and protein degradation by proteasome, regulates cellular NOXA levels from low in steady state to rapidly enhanced upon stressful condition. Antimitotics and proteasome inhibitors are powerful anticancer treatments that mainly rely on NOXA activity to trigger death in cancer cells. In addition, in case of antimitotics, a wave of cell death based on NOXA and fueled by an automomous secretome spreads through the tumor, revealing new therapeutic opportunities. By neutralizing MCL-1 prosurvival activity, NOXA induces preferential BCL-2 or BCL-xL cancer cell survival dependencies, that can be exploited therapeutically using BH3 mimetics. Since MCL-1 interfers with tumor response to chemotherapies, promoting NOXA expression or using recently available MCL-1 targeting BH3 mimetics are promising opportunities to improve cancer treatments.

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