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Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer
Cancer cells experience unique and dynamic shifts in their metabolic function in order to survive, proliferate, and evade growth inhibition in the resource-scarce tumor microenvironment. Therefore, identification of pharmacological agents with potential to reprogram cancer cell metabolism may improv...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674637/ https://www.ncbi.nlm.nih.gov/pubmed/33224954 http://dx.doi.org/10.3389/fcell.2020.590192 |
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author | Cozzo, Alyssa J. Coleman, Michael F. Pearce, Jane B. Pfeil, Alexander J. Etigunta, Suhas K. Hursting, Stephen D. |
author_facet | Cozzo, Alyssa J. Coleman, Michael F. Pearce, Jane B. Pfeil, Alexander J. Etigunta, Suhas K. Hursting, Stephen D. |
author_sort | Cozzo, Alyssa J. |
collection | PubMed |
description | Cancer cells experience unique and dynamic shifts in their metabolic function in order to survive, proliferate, and evade growth inhibition in the resource-scarce tumor microenvironment. Therefore, identification of pharmacological agents with potential to reprogram cancer cell metabolism may improve clinical outcomes in cancer therapy. Cancer cells also often exhibit an increased dependence on the process known as autophagy, both for baseline survival and as a response to stressors such as chemotherapy or a decline in nutrient availability. There is evidence to suggest that this increased dependence on autophagy in cancer cells may be exploitable clinically by combining autophagy modulators with existing chemotherapies. In light of the increased metabolic rate in cancer cells, interest is growing in approaches aimed at “starving” cancer through dietary and pharmacologic interventions that reduce availability of nutrients and pro-growth hormonal signals known to promote cancer progression. Several dietary approaches, including chronic calorie restriction and multiple forms of fasting, have been investigated for their potential anti-cancer benefits, yielding promising results in animal models. Induction of autophagy in response to dietary energy restriction may underlie some of the observed benefit. However, while interventions based on dietary energy restriction have demonstrated safety in clinical trials, uncertainty remains regarding translation to humans as well as feasibility of achieving compliance due to the potential discomfort and weight loss that accompanies dietary restriction. Further induction of autophagy through dietary or pharmacologic metabolic reprogramming interventions may enhance the efficacy of autophagy inhibition in the context of adjuvant or neo-adjuvant chemotherapy. Nonetheless, it remains unclear whether therapeutic agents aimed at autophagy induction, autophagy inhibition, or both are a viable therapeutic strategy for improving cancer outcomes. This review discusses the literature available for the therapeutic potential of these approaches. |
format | Online Article Text |
id | pubmed-7674637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76746372020-11-19 Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer Cozzo, Alyssa J. Coleman, Michael F. Pearce, Jane B. Pfeil, Alexander J. Etigunta, Suhas K. Hursting, Stephen D. Front Cell Dev Biol Cell and Developmental Biology Cancer cells experience unique and dynamic shifts in their metabolic function in order to survive, proliferate, and evade growth inhibition in the resource-scarce tumor microenvironment. Therefore, identification of pharmacological agents with potential to reprogram cancer cell metabolism may improve clinical outcomes in cancer therapy. Cancer cells also often exhibit an increased dependence on the process known as autophagy, both for baseline survival and as a response to stressors such as chemotherapy or a decline in nutrient availability. There is evidence to suggest that this increased dependence on autophagy in cancer cells may be exploitable clinically by combining autophagy modulators with existing chemotherapies. In light of the increased metabolic rate in cancer cells, interest is growing in approaches aimed at “starving” cancer through dietary and pharmacologic interventions that reduce availability of nutrients and pro-growth hormonal signals known to promote cancer progression. Several dietary approaches, including chronic calorie restriction and multiple forms of fasting, have been investigated for their potential anti-cancer benefits, yielding promising results in animal models. Induction of autophagy in response to dietary energy restriction may underlie some of the observed benefit. However, while interventions based on dietary energy restriction have demonstrated safety in clinical trials, uncertainty remains regarding translation to humans as well as feasibility of achieving compliance due to the potential discomfort and weight loss that accompanies dietary restriction. Further induction of autophagy through dietary or pharmacologic metabolic reprogramming interventions may enhance the efficacy of autophagy inhibition in the context of adjuvant or neo-adjuvant chemotherapy. Nonetheless, it remains unclear whether therapeutic agents aimed at autophagy induction, autophagy inhibition, or both are a viable therapeutic strategy for improving cancer outcomes. This review discusses the literature available for the therapeutic potential of these approaches. Frontiers Media S.A. 2020-11-05 /pmc/articles/PMC7674637/ /pubmed/33224954 http://dx.doi.org/10.3389/fcell.2020.590192 Text en Copyright © 2020 Cozzo, Coleman, Pearce, Pfeil, Etigunta and Hursting. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Cozzo, Alyssa J. Coleman, Michael F. Pearce, Jane B. Pfeil, Alexander J. Etigunta, Suhas K. Hursting, Stephen D. Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer |
title | Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer |
title_full | Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer |
title_fullStr | Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer |
title_full_unstemmed | Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer |
title_short | Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer |
title_sort | dietary energy modulation and autophagy: exploiting metabolic vulnerabilities to starve cancer |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674637/ https://www.ncbi.nlm.nih.gov/pubmed/33224954 http://dx.doi.org/10.3389/fcell.2020.590192 |
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