Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Bestion, Eloïne, Raymond, Eric, Mezouar, Soraya, Halfon, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785072216190222336
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
work_keys_str_mv AT bestioneloine updateonautophagyinhibitorsincanceropeninguptoatherapeuticcombinationwithimmunecheckpointinhibitors
AT raymonderic updateonautophagyinhibitorsincanceropeninguptoatherapeuticcombinationwithimmunecheckpointinhibitors
AT mezouarsoraya updateonautophagyinhibitorsincanceropeninguptoatherapeuticcombinationwithimmunecheckpointinhibitors
AT halfonphilippe updateonautophagyinhibitorsincanceropeninguptoatherapeuticcombinationwithimmunecheckpointinhibitors