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Update on Autophagy Inhibitors in Cancer: Opening up to a Therapeutic Combination with Immune Checkpoint Inhibitors
Autophagy is a highly conserved and natural degradation process that helps maintain cell homeostasis through the elimination of old, worn, and defective cellular components, ensuring proper cell energy intake. The degradative pathway constitutes a protective barrier against diverse human diseases in...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341243/ https://www.ncbi.nlm.nih.gov/pubmed/37443736 http://dx.doi.org/10.3390/cells12131702 |
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author | Bestion, Eloïne Raymond, Eric Mezouar, Soraya Halfon, Philippe |
author_facet | Bestion, Eloïne Raymond, Eric Mezouar, Soraya Halfon, Philippe |
author_sort | Bestion, Eloïne |
collection | PubMed |
description | Autophagy is a highly conserved and natural degradation process that helps maintain cell homeostasis through the elimination of old, worn, and defective cellular components, ensuring proper cell energy intake. The degradative pathway constitutes a protective barrier against diverse human diseases including cancer. Autophagy basal level has been reported to be completely dysregulated during the entire oncogenic process. Autophagy influences not only cancer initiation, development, and maintenance but also regulates cancer response to therapy. Currently, autophagy inhibitor candidates mainly target the early autophagy process without any successful preclinical/clinical development. Lessons learned from autophagy pharmaceutical manipulation as a curative option progressively help to improve drug design and to encounter new targets of interest. Combinatorial strategies with autophagy modulators are supported by abundant evidence, especially dealing with immune checkpoint inhibitors, for which encouraging preclinical results have been recently published. GNS561, a PPT1 inhibitor, is a promising autophagy modulator as it has started a phase 2 clinical trial in liver cancer indication, combined with atezolizumab and bevacizumab, an assessment without precedent in the field. This approach paves a new road, leading to the resurgence of anticancer autophagy inhibitors as an attractive therapeutic target in cancer. |
format | Online Article Text |
id | pubmed-10341243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103412432023-07-14 Update on Autophagy Inhibitors in Cancer: Opening up to a Therapeutic Combination with Immune Checkpoint Inhibitors Bestion, Eloïne Raymond, Eric Mezouar, Soraya Halfon, Philippe Cells Review Autophagy is a highly conserved and natural degradation process that helps maintain cell homeostasis through the elimination of old, worn, and defective cellular components, ensuring proper cell energy intake. The degradative pathway constitutes a protective barrier against diverse human diseases including cancer. Autophagy basal level has been reported to be completely dysregulated during the entire oncogenic process. Autophagy influences not only cancer initiation, development, and maintenance but also regulates cancer response to therapy. Currently, autophagy inhibitor candidates mainly target the early autophagy process without any successful preclinical/clinical development. Lessons learned from autophagy pharmaceutical manipulation as a curative option progressively help to improve drug design and to encounter new targets of interest. Combinatorial strategies with autophagy modulators are supported by abundant evidence, especially dealing with immune checkpoint inhibitors, for which encouraging preclinical results have been recently published. GNS561, a PPT1 inhibitor, is a promising autophagy modulator as it has started a phase 2 clinical trial in liver cancer indication, combined with atezolizumab and bevacizumab, an assessment without precedent in the field. This approach paves a new road, leading to the resurgence of anticancer autophagy inhibitors as an attractive therapeutic target in cancer. MDPI 2023-06-23 /pmc/articles/PMC10341243/ /pubmed/37443736 http://dx.doi.org/10.3390/cells12131702 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Bestion, Eloïne Raymond, Eric Mezouar, Soraya Halfon, Philippe Update on Autophagy Inhibitors in Cancer: Opening up to a Therapeutic Combination with Immune Checkpoint Inhibitors |
title | Update on Autophagy Inhibitors in Cancer: Opening up to a Therapeutic Combination with Immune Checkpoint Inhibitors |
title_full | Update on Autophagy Inhibitors in Cancer: Opening up to a Therapeutic Combination with Immune Checkpoint Inhibitors |
title_fullStr | Update on Autophagy Inhibitors in Cancer: Opening up to a Therapeutic Combination with Immune Checkpoint Inhibitors |
title_full_unstemmed | Update on Autophagy Inhibitors in Cancer: Opening up to a Therapeutic Combination with Immune Checkpoint Inhibitors |
title_short | Update on Autophagy Inhibitors in Cancer: Opening up to a Therapeutic Combination with Immune Checkpoint Inhibitors |
title_sort | update on autophagy inhibitors in cancer: opening up to a therapeutic combination with immune checkpoint inhibitors |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341243/ https://www.ncbi.nlm.nih.gov/pubmed/37443736 http://dx.doi.org/10.3390/cells12131702 |
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