Starvation Based Differential Chemotherapy: A Novel Approach for Cancer Treatment

Abstract

Cancer patients undergoing chemotherapy treatment are advised to increase food intake to overcome the therapy-induced side effects, and weight loss. Dietary restriction is known to slow down the aging process and hence reduce age-related diseases such as cancer. Fasting or short-term starvation is more effective than dietary restriction to prevent cancer growth since starved cells switch off signals for growth and reproduction and enter a protective mode, while cancer cells, being mutated, are not sensitized by any external growth signals and are not protected against any stress. This phenomenon is known as differential stress resistance (DSR). Nutrient signaling pathways involving growth hormone/insulin-like growth factor-1 axis and its downstream effectors, play a key role in DSR in response to starvation controlling the other cell maintenance systems, such as autophagy and apoptosis, that are related to the tumorigenesis. Yeast cells lacking these effectors are better protected against oxidative stress compared to normal cells. In the same way, starvation protects many cell lines and mice against high-dose chemotherapeutic drugs. According to a series of studies, fasting results in overall reduction in chemotherapy side effects in cancer patients. Data shows that starvation-dependent differential chemotherapy is safe, feasible and effective in cancer treatment, but the possible side effects of starvation limit its efficacy. However, further studies and clinical trials may result in its implementation in cancer treatment.

Dichloroacetate enhances the antitumor efficacy of chemotherapeutic agents via inhibiting autophagy in non-small-cell lung cancer

“…Stress-induced autophagy is an important protective strategy that can maintain cell survival, which ultimately results in drug resistance in various types of tumor cells. 38 In this study, DCA treatment inhibited cellular autophagy and promoted apoptosis. RARA, an autophagy activator, can render the cells more resistant to DCA, indicating that DCA causes cell death by disrupting cancer cell metabolism and inhibiting autophagy.…”

Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy

“…Autophagy is an evolutionarily conserved catabolic pathway where cells deliver their own cytoplasmic material and/or organelles to lysosomes for degradation[ 9 ]. Accumulating evidence shows that the increased level of autophagy induced by chemotherapy contributes to tumor MDR[ 24 ]. Autophagy serves as an adaptive stress response in tumor cells that facilitates their survival in settings of increased metabolic demand, hypoxic microenvironments, or cancer therapies[ 25 ].…”

Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans

“…Previous studies also showed that tumor suppressor genes, daf-16/ Foxo, daf-18/Pten, and lin-35/Rb are required for promoting C. elegans starvation survival (Baugh and Sternberg 2006;Cui et al 2013). Starvation or fasting has recently been investigated in cancer therapy (Naveed et al 2014;Cangemi et al 2016), as tumor cells are thought to be more susceptible to starvation due to the Warburg effect (Iansante et al 2015). Results from this study and previous work using C. elegans may suggest that cancer cells, that commonly harbor mutations in tumor suppressor genes, are highly sensitive to starvation stress.…”