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The Switch between Protective and Nonprotective Autophagy; Implications for Autophagy Inhibition as a Therapeutic Strategy in Cancer

Autophagy, a process of cellular self-degradation and cell survival whereby the cell generates energy and metabolic intermediates under conditions of stress (i.e., nutrient deprivation), is also commonly induced in tumor cells in response to chemotherapy and radiation. While chemotherapy-induced aut...

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Autor principal: Gewirtz, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168293/
https://www.ncbi.nlm.nih.gov/pubmed/31947952
http://dx.doi.org/10.3390/biology9010012
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author Gewirtz, David A.
author_facet Gewirtz, David A.
author_sort Gewirtz, David A.
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description Autophagy, a process of cellular self-degradation and cell survival whereby the cell generates energy and metabolic intermediates under conditions of stress (i.e., nutrient deprivation), is also commonly induced in tumor cells in response to chemotherapy and radiation. While chemotherapy-induced autophagy and radiation-induced autophagy are generally considered to have cytoprotective functions, thereby reducing tumor cell sensitivity (and potentially conferring resistance) to various treatment modalities, autophagy can also be nonprotective; furthermore, the nature of the autophagy can be altered via the “autophagic switch” depending on such factors as the p53 status of the tumor cells. Defective or compromised autophagy has also been associated with neurodegenerative diseases, raising concerns as to the impact of autophagy inhibition on normal tissue function. Furthermore, the impact of autophagy inhibition on the immune system response to therapy as well as the influence of autophagy inhibition in combination with chemotherapy or radiation on critical tissue sites such as the bone marrow remain uncertain. These are factors requiring serious consideration within the context of current clinical efforts to exploit autophagy inhibition as a therapeutic strategy in cancer.
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spelling pubmed-71682932020-04-22 The Switch between Protective and Nonprotective Autophagy; Implications for Autophagy Inhibition as a Therapeutic Strategy in Cancer Gewirtz, David A. Biology (Basel) Opinion Autophagy, a process of cellular self-degradation and cell survival whereby the cell generates energy and metabolic intermediates under conditions of stress (i.e., nutrient deprivation), is also commonly induced in tumor cells in response to chemotherapy and radiation. While chemotherapy-induced autophagy and radiation-induced autophagy are generally considered to have cytoprotective functions, thereby reducing tumor cell sensitivity (and potentially conferring resistance) to various treatment modalities, autophagy can also be nonprotective; furthermore, the nature of the autophagy can be altered via the “autophagic switch” depending on such factors as the p53 status of the tumor cells. Defective or compromised autophagy has also been associated with neurodegenerative diseases, raising concerns as to the impact of autophagy inhibition on normal tissue function. Furthermore, the impact of autophagy inhibition on the immune system response to therapy as well as the influence of autophagy inhibition in combination with chemotherapy or radiation on critical tissue sites such as the bone marrow remain uncertain. These are factors requiring serious consideration within the context of current clinical efforts to exploit autophagy inhibition as a therapeutic strategy in cancer. MDPI 2020-01-04 /pmc/articles/PMC7168293/ /pubmed/31947952 http://dx.doi.org/10.3390/biology9010012 Text en © 2020 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Opinion
Gewirtz, David A.
The Switch between Protective and Nonprotective Autophagy; Implications for Autophagy Inhibition as a Therapeutic Strategy in Cancer
title The Switch between Protective and Nonprotective Autophagy; Implications for Autophagy Inhibition as a Therapeutic Strategy in Cancer
title_full The Switch between Protective and Nonprotective Autophagy; Implications for Autophagy Inhibition as a Therapeutic Strategy in Cancer
title_fullStr The Switch between Protective and Nonprotective Autophagy; Implications for Autophagy Inhibition as a Therapeutic Strategy in Cancer
title_full_unstemmed The Switch between Protective and Nonprotective Autophagy; Implications for Autophagy Inhibition as a Therapeutic Strategy in Cancer
title_short The Switch between Protective and Nonprotective Autophagy; Implications for Autophagy Inhibition as a Therapeutic Strategy in Cancer
title_sort switch between protective and nonprotective autophagy; implications for autophagy inhibition as a therapeutic strategy in cancer
topic Opinion
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168293/
https://www.ncbi.nlm.nih.gov/pubmed/31947952
http://dx.doi.org/10.3390/biology9010012
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