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Review
. 2016 Nov 14;6:242.
doi: 10.3389/fonc.2016.00242. eCollection 2016.

Enhanced Therapeutic Efficacy in Cancer Patients by Short-term Fasting: The Autophagy Connection

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Free PMC article
Review

Enhanced Therapeutic Efficacy in Cancer Patients by Short-term Fasting: The Autophagy Connection

Gustav van Niekerk et al. Front Oncol. .
Free PMC article

Abstract

Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy toward cell maintenance and repair processes, rather than growth and proliferation. However, fasting is also known to upregulate autophagy, an evolutionarily conserved catabolic process that is upregulated in response to various cell stressors. Here, we review a number of mechanisms by which fasting-induced autophagy may have an impact on both chemo-tolerance and chemo-sensitization. First, fasting may exert a protective effect by mobilizing autophagic components prior to chemo-induction. In turn, the autophagic apparatus can be repurposed for removing cellular components damaged by chemotherapy. Autophagy also plays a key role in epitope expression as well as in modulating inflammation. Chemo-sensitization resulting from fasting may in fact be an effect of enhanced immune surveillance as a result of better autophagy-dependent epitope processing. Finally, autophagy is involved in host defense against viruses, and aspects of the autophagic process are also often targets for viral subversion. Consequently, altering autophagic flux by fasting may alter viral infectivity. These observations suggest that fasting-induced autophagy may have an impact on therapeutic efficacy in various oncological contexts.

Keywords: autophagy; chemotherapy; fasting; immunogenic cell death; oncolytic virus.

Figures

Figure 1
Figure 1
Autophagy may remove cellular components damaged by antineoplastic therapies and also promote the reinstatement of immune surveillance against cancer cells. (A) Autophagy plays a key role in the clearance of damaged cellular components and organelles. Removal of protein aggregates or damaged mitochondria may promote cell survival. (B) Autophagy is also involved in epitope expression. Exogenous antigens derived from cell bodies or secreted by cancer cells can be processed into epitopes to be loaded in MHC I and II loading compartments. Similarly, endogenous epitopes processed by autophagy can be expressed by cancer cells, enhancing their immunogenic profile. (C) Fasting may also have an impact on the efficacy of oncolytic viral therapy. Many viruses target diverse steps within the autophagic process for either viral subversion or inhibition of host antiviral response [reviewed by Chiramel et al. (42)]. Thus, autophagy may either promote or impede viral infectivity. Not illustrated, autophagy has also been implicated in the release of inflammatory mediators, such as IL-1β, ATP, and HMGB1, via secretory autophagy (26).

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