Cargando…

In Vivo Anticancer Activity of AZD3965: A Systematic Review

Proliferating cancer cells have high energy demands, which is mainly obtained through glycolysis. The transmembrane trafficking of lactate, a major metabolite produced by glycolytic cancer cells, relies on monocarboxylate transporters (MCTs). MCT1 optimally imports lactate, although it can work bidi...

Descripción completa

Detalles Bibliográficos
Autores principales: Silva, Ana, Antunes, Beatriz, Batista, Alberta, Pinto-Ribeiro, Filipa, Baltazar, Fátima, Afonso, Julieta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746498/
https://www.ncbi.nlm.nih.gov/pubmed/35011413
http://dx.doi.org/10.3390/molecules27010181
_version_ 1784630601062547456
author Silva, Ana
Antunes, Beatriz
Batista, Alberta
Pinto-Ribeiro, Filipa
Baltazar, Fátima
Afonso, Julieta
author_facet Silva, Ana
Antunes, Beatriz
Batista, Alberta
Pinto-Ribeiro, Filipa
Baltazar, Fátima
Afonso, Julieta
author_sort Silva, Ana
collection PubMed
description Proliferating cancer cells have high energy demands, which is mainly obtained through glycolysis. The transmembrane trafficking of lactate, a major metabolite produced by glycolytic cancer cells, relies on monocarboxylate transporters (MCTs). MCT1 optimally imports lactate, although it can work bidirectionally, and its activity has been linked to cancer aggressiveness and poor outcomes. AZD3965, a specific MCT1 inhibitor, was tested both in vitro and in vivo, with encouraging results; a phase I clinical trial has already been undertaken. Thus, analysis of the experimental evidence using AZD3965 in different cancer types could give valuable information for its clinical use. This systematic review aimed to assess the in vivo anticancer activity of AZD3965 either alone (monotherapy) or with other interventions (combination therapy). Study search was performed in nine different databases using the keywords “AZD3965 in vivo” as search terms. The results show that AZD3965 successfully decreased tumor growth and promoted intracellular lactate accumulation, which confirmed its effectiveness, especially in combined therapy. These results support the setup of clinical trials, but other important findings, namely AZD3965 enhanced activity when given in combination with other therapies, or MCT4-induced treatment resistance, should be further considered in the clinical trial design to improve therapy response.
format Online
Article
Text
id pubmed-8746498
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87464982022-01-11 In Vivo Anticancer Activity of AZD3965: A Systematic Review Silva, Ana Antunes, Beatriz Batista, Alberta Pinto-Ribeiro, Filipa Baltazar, Fátima Afonso, Julieta Molecules Systematic Review Proliferating cancer cells have high energy demands, which is mainly obtained through glycolysis. The transmembrane trafficking of lactate, a major metabolite produced by glycolytic cancer cells, relies on monocarboxylate transporters (MCTs). MCT1 optimally imports lactate, although it can work bidirectionally, and its activity has been linked to cancer aggressiveness and poor outcomes. AZD3965, a specific MCT1 inhibitor, was tested both in vitro and in vivo, with encouraging results; a phase I clinical trial has already been undertaken. Thus, analysis of the experimental evidence using AZD3965 in different cancer types could give valuable information for its clinical use. This systematic review aimed to assess the in vivo anticancer activity of AZD3965 either alone (monotherapy) or with other interventions (combination therapy). Study search was performed in nine different databases using the keywords “AZD3965 in vivo” as search terms. The results show that AZD3965 successfully decreased tumor growth and promoted intracellular lactate accumulation, which confirmed its effectiveness, especially in combined therapy. These results support the setup of clinical trials, but other important findings, namely AZD3965 enhanced activity when given in combination with other therapies, or MCT4-induced treatment resistance, should be further considered in the clinical trial design to improve therapy response. MDPI 2021-12-29 /pmc/articles/PMC8746498/ /pubmed/35011413 http://dx.doi.org/10.3390/molecules27010181 Text en © 2021 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 Systematic Review
Silva, Ana
Antunes, Beatriz
Batista, Alberta
Pinto-Ribeiro, Filipa
Baltazar, Fátima
Afonso, Julieta
In Vivo Anticancer Activity of AZD3965: A Systematic Review
title In Vivo Anticancer Activity of AZD3965: A Systematic Review
title_full In Vivo Anticancer Activity of AZD3965: A Systematic Review
title_fullStr In Vivo Anticancer Activity of AZD3965: A Systematic Review
title_full_unstemmed In Vivo Anticancer Activity of AZD3965: A Systematic Review
title_short In Vivo Anticancer Activity of AZD3965: A Systematic Review
title_sort in vivo anticancer activity of azd3965: a systematic review
topic Systematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746498/
https://www.ncbi.nlm.nih.gov/pubmed/35011413
http://dx.doi.org/10.3390/molecules27010181
work_keys_str_mv AT silvaana invivoanticanceractivityofazd3965asystematicreview
AT antunesbeatriz invivoanticanceractivityofazd3965asystematicreview
AT batistaalberta invivoanticanceractivityofazd3965asystematicreview
AT pintoribeirofilipa invivoanticanceractivityofazd3965asystematicreview
AT baltazarfatima invivoanticanceractivityofazd3965asystematicreview
AT afonsojulieta invivoanticanceractivityofazd3965asystematicreview