Cancer and Fasting: Can Fasting/Calorie Restriction (CR) or Fasting-Mimicking Diet (FMD) Help Fight Cancer? Molecular Basis of Fasting Response

Abstract

The ecosystem of cancer management is exploring the multiple approaches for the effective management of cancer. In the quest of integrated cancer management, the beneficial therapeutic effects of fasting/calorie restriction (CR) or fasting-mimicking diet (FMD) have inspired researchers and clinicians owing to their benefits to cancer patients towards overall survival, disease prevention, improvements in treatments and amelioration of side effects and off-target toxicities. There are growing preclinical clinical evidences, which describe the anticancer effects of fasting/CR or FMD by reducing cancer progression, inducing the mortality of cancer cells and improving the effectiveness and tolerability of chemo- and radiotherapies. Series of clinical trials are being launched and several completed (ClinicalTrials.gov) for addressing the interventions of fasting/CR or FMD in caner management; however, the overall outcome of studies seems to be inconsistent and perhaps focused randomized clinical trials are still required to understand their multidimensional molecular effects under different settings of cancer therapy. As a part of understanding the molecular basis of fasting/CR or FMD, the experimental data indicate that fasting/CR or FMDs significantly deplete the levels of tumour growth essential nutrients and factors, including glucose, IGF1 and insulin. Apart from significant decrease in the ratio of ATP/ADP and NADH/NAD, there is upregulation of variety of proteins, which are involved in apoptosis, autophagy, detoxification, DNA repair, genomic stability and immunosurveillance, while several proteins and pathways implicated in cell proliferation and oxidative damage are downregulated. Interestingly, fasting/CR or FMD may demonstrate altogether different and even opposite effects in different cancer cell types or even within the same cancer cell type.