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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...

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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
Descripción
Sumario: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.