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Ligands stimulating antitumour immunity as the next G-quadruplex challenge
G-quadruplex (G4) binders have been investigated to discover new anticancer drugs worldwide in past decades. As these ligands are generally not highly cytotoxic, the discovery rational was mainly based on increasing the cell-killing potency. Nevertheless, no G4 binder has been shown yet to be effect...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482198/ https://www.ncbi.nlm.nih.gov/pubmed/36114513 http://dx.doi.org/10.1186/s12943-022-01649-y |
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author | Miglietta, Giulia Marinello, Jessica Russo, Marco Capranico, Giovanni |
author_facet | Miglietta, Giulia Marinello, Jessica Russo, Marco Capranico, Giovanni |
author_sort | Miglietta, Giulia |
collection | PubMed |
description | G-quadruplex (G4) binders have been investigated to discover new anticancer drugs worldwide in past decades. As these ligands are generally not highly cytotoxic, the discovery rational was mainly based on increasing the cell-killing potency. Nevertheless, no G4 binder has been shown yet to be effective in cancer patients. Here, G4 binder activity at low dosages will be discussed as a critical feature to discover ligands with therapeutic effects in cancer patients. Specific effects of G4 binders al low doses have been reported to occur in cancer and normal cells. Among them, genome instability and the stimulation of cytoplasmic processes related to autophagy and innate immune response open to the use of G4 binders as immune-stimulating agents. Thus, we propose a new rational of drug discovery, which is not based on cytotoxic potency but rather on immune gene activation at non-cytotoxic dosage. |
format | Online Article Text |
id | pubmed-9482198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-94821982022-09-18 Ligands stimulating antitumour immunity as the next G-quadruplex challenge Miglietta, Giulia Marinello, Jessica Russo, Marco Capranico, Giovanni Mol Cancer Review G-quadruplex (G4) binders have been investigated to discover new anticancer drugs worldwide in past decades. As these ligands are generally not highly cytotoxic, the discovery rational was mainly based on increasing the cell-killing potency. Nevertheless, no G4 binder has been shown yet to be effective in cancer patients. Here, G4 binder activity at low dosages will be discussed as a critical feature to discover ligands with therapeutic effects in cancer patients. Specific effects of G4 binders al low doses have been reported to occur in cancer and normal cells. Among them, genome instability and the stimulation of cytoplasmic processes related to autophagy and innate immune response open to the use of G4 binders as immune-stimulating agents. Thus, we propose a new rational of drug discovery, which is not based on cytotoxic potency but rather on immune gene activation at non-cytotoxic dosage. BioMed Central 2022-09-17 /pmc/articles/PMC9482198/ /pubmed/36114513 http://dx.doi.org/10.1186/s12943-022-01649-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Miglietta, Giulia Marinello, Jessica Russo, Marco Capranico, Giovanni Ligands stimulating antitumour immunity as the next G-quadruplex challenge |
title | Ligands stimulating antitumour immunity as the next G-quadruplex challenge |
title_full | Ligands stimulating antitumour immunity as the next G-quadruplex challenge |
title_fullStr | Ligands stimulating antitumour immunity as the next G-quadruplex challenge |
title_full_unstemmed | Ligands stimulating antitumour immunity as the next G-quadruplex challenge |
title_short | Ligands stimulating antitumour immunity as the next G-quadruplex challenge |
title_sort | ligands stimulating antitumour immunity as the next g-quadruplex challenge |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482198/ https://www.ncbi.nlm.nih.gov/pubmed/36114513 http://dx.doi.org/10.1186/s12943-022-01649-y |
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