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Fasting-induced metabolic reprogramming as a therapeutic vulnerability in cancer: a systematic mechanistic review of in vitro evidence.

Created on 26 Sep 2026

Authors

Rihab Bensalek, Hind Hassani Idrissi, Atmane Ait Baha, Meryem Hicham, Omar Akhouayri, Mouna Habbane, Bouchra Benazzouz

Published in

Medical oncology (Northwood, London, England). Volume 43. Issue 11. Sep 25, 2026. Epub Sep 25, 2026.

Abstract

Fasting and fasting-mimicking interventions have emerged as promising metabolic strategies in oncology. While preclinical evidence suggests enhanced tumor sensitivity to therapy, the mechanistic basis of fasting-induced anticancer effects remains incompletely defined. To systematically evaluate and synthesize in vitro evidence investigating the molecular and metabolic impact of fasting-based interventions on cancer cell models. A systematic review was conducted following PRISMA guidelines. Eligible studies investigated fasting-mimicking conditions, serum starvation or nutrient restriction in cancer cell lines. Risk of bias was assessed across predefined methodological domains. Eleven studies met inclusion criteria. Across diverse tumor types, fasting conditions consistently reduced IGF-1 signaling, inhibited PI3K/AKT/mTOR pathways, suppressed glycolysis, and induced AMPK-mediated stress responses. Cancer cells exhibited impaired proliferative capacity and increased sensitivity to chemotherapeutic agents under nutrient restriction. Despite methodological heterogeneity, mechanistic convergence across independent models was notable. Fasting induces a coordinated metabolic reprogramming that exposes intrinsic anabolic dependencies of malignant cells. These findings support the concept of fasting as a systems-level metabolic vulnerability strategy and warrant standardized translational investigation.

PMID:
42789187
Bibliographic data and abstract were imported from PubMed on 26 Sep 2026.

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