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Autophagy modulation: a prudent approach in cancer treatment?

Autophagy is a tightly controlled process comprising lysosomal degradation and recycling of cellular proteins and organelles. In cancer, its paradoxical dual role of cytoprotection and cytotoxicity is context-dependent and controversial. Autophagy primarily acts as a mechanism of tumour suppression,...

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Autores principales: Bishop, Eleanor, Bradshaw, Tracey D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267659/
https://www.ncbi.nlm.nih.gov/pubmed/30182146
http://dx.doi.org/10.1007/s00280-018-3669-6
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author Bishop, Eleanor
Bradshaw, Tracey D.
author_facet Bishop, Eleanor
Bradshaw, Tracey D.
author_sort Bishop, Eleanor
collection PubMed
description Autophagy is a tightly controlled process comprising lysosomal degradation and recycling of cellular proteins and organelles. In cancer, its paradoxical dual role of cytoprotection and cytotoxicity is context-dependent and controversial. Autophagy primarily acts as a mechanism of tumour suppression, by maintenance of genomic integrity and prevention of proliferation and inflammation. This, combined with immune-surveillance capabilities and autophagy’s implicated role in cell death, acts to prevent tumour initiation. However, established tumours exploit autophagy to survive cellular stresses in the hostile tumour microenvironment. This can lead to therapy resistance, one of the biggest challenges facing current anti-cancer approaches. Autophagy modulation is an exciting area of clinical development, attempting to harness this fundamental process as an anti-cancer strategy. Autophagy induction could potentially prevent tumour formation and enhance anti-cancer immune responses. In addition, drug-induced autophagy could be used to kill cancer cells, particularly those in which the apoptotic machinery is defective. Conversely, autophagy inhibition may help to sensitise resistant cancer cells to conventional chemotherapies and specifically target autophagy-addicted tumours. Currently, hydroxychloroquine is in phase I and II clinical trials in combination with several standard chemotherapies, whereas direct, deliberate autophagy induction remains to be tested clinically. More comprehensive understanding of the roles of autophagy throughout different stages of carcinogenesis has potential to guide development of novel therapeutic strategies to eradicate cancer cells.
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spelling pubmed-62676592018-12-18 Autophagy modulation: a prudent approach in cancer treatment? Bishop, Eleanor Bradshaw, Tracey D. Cancer Chemother Pharmacol Review Article Autophagy is a tightly controlled process comprising lysosomal degradation and recycling of cellular proteins and organelles. In cancer, its paradoxical dual role of cytoprotection and cytotoxicity is context-dependent and controversial. Autophagy primarily acts as a mechanism of tumour suppression, by maintenance of genomic integrity and prevention of proliferation and inflammation. This, combined with immune-surveillance capabilities and autophagy’s implicated role in cell death, acts to prevent tumour initiation. However, established tumours exploit autophagy to survive cellular stresses in the hostile tumour microenvironment. This can lead to therapy resistance, one of the biggest challenges facing current anti-cancer approaches. Autophagy modulation is an exciting area of clinical development, attempting to harness this fundamental process as an anti-cancer strategy. Autophagy induction could potentially prevent tumour formation and enhance anti-cancer immune responses. In addition, drug-induced autophagy could be used to kill cancer cells, particularly those in which the apoptotic machinery is defective. Conversely, autophagy inhibition may help to sensitise resistant cancer cells to conventional chemotherapies and specifically target autophagy-addicted tumours. Currently, hydroxychloroquine is in phase I and II clinical trials in combination with several standard chemotherapies, whereas direct, deliberate autophagy induction remains to be tested clinically. More comprehensive understanding of the roles of autophagy throughout different stages of carcinogenesis has potential to guide development of novel therapeutic strategies to eradicate cancer cells. Springer Berlin Heidelberg 2018-09-04 2018 /pmc/articles/PMC6267659/ /pubmed/30182146 http://dx.doi.org/10.1007/s00280-018-3669-6 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review Article
Bishop, Eleanor
Bradshaw, Tracey D.
Autophagy modulation: a prudent approach in cancer treatment?
title Autophagy modulation: a prudent approach in cancer treatment?
title_full Autophagy modulation: a prudent approach in cancer treatment?
title_fullStr Autophagy modulation: a prudent approach in cancer treatment?
title_full_unstemmed Autophagy modulation: a prudent approach in cancer treatment?
title_short Autophagy modulation: a prudent approach in cancer treatment?
title_sort autophagy modulation: a prudent approach in cancer treatment?
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267659/
https://www.ncbi.nlm.nih.gov/pubmed/30182146
http://dx.doi.org/10.1007/s00280-018-3669-6
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