Plain language summary
Autophagy is a cellular mechanism that removes unnecessary or dysfunctional components and is being studied intensively with regards to chronic disease, including cancer. Dietary restriction, as in intermittent fasting, is thought to activate autophagy. The authors review the literature and possible mechanisms for autophagy in cancer, noting that autophagy can both suppress and support cancer development and growth. It appears that fasting in combination with cytotoxic drugs elicits differential responses in normal and cancer cells, whereby normal cells prioritise maintenance pathways and inactivate growth factor signalling when nutrients are absent, whilst cancer cells, do not inhibit stress resistance pathways, thus becoming vulnerable to cytotoxic treatment Preclinical studies on calorie restriction or intermittent fasting in combination with chemo- and/or radiotherapy have found beneficial effects in animal and in vitro studies. There are a number of clinical human trials underway, but only two completed pilot trials, which showed promising results with reducing side effects and increasing efficacy of the chemotherapeutic drugs through intermittent fasting.
Cancer is a leading cause of death worldwide, and its incidence is continually increasing. Although anticancer therapy has improved significantly, it still has limited efficacy for tumor eradication and is highly toxic to healthy cells. Thus, novel therapeutic strategies to improve chemotherapy, radiotherapy and targeted therapy are an important goal in cancer research. Macroautophagy (herein referred to as autophagy) is a conserved lysosomal degradation pathway for the intracellular recycling of macromolecules and clearance of damaged organelles and misfolded proteins to ensure cellular homeostasis. Dysfunctional autophagy contributes to many diseases, including cancer. Autophagy can suppress or promote tumors depending on the developmental stage and tumor type, and modulating autophagy for cancer treatment is an interesting therapeutic approach currently under intense investigation. Nutritional restriction is a promising protocol to modulate autophagy and enhance the efficacy of anticancer therapies while protecting normal cells. Here, the description and role of autophagy in tumorigenesis will be summarized. Moreover, the possibility of using fasting as an adjuvant therapy for cancer treatment, as well as the molecular mechanisms underlying this approach, will be presented.