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In Vivo Anticancer Activity of AZD3965: A Systematic Review

Authors :
Ana Silva
Beatriz Antunes
Alberta Batista
Filipa Pinto-Ribeiro
Fátima Baltazar
Julieta Afonso
Source :
Molecules, Vol 27, Iss 1, p 181 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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.

Details

Language :
English
ISSN :
14203049
Volume :
27
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.89ed9e1e6ede4364ad18b79349f1bc13
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules27010181