In vivo anticancer activity of AZD3965: a systematic review

Detalhes bibliográficos
Autor(a) principal: Silva, Ana
Data de Publicação: 2022
Outros Autores: Antunes, Beatriz, Batista, Alberta, Pinto-Ribeiro, Filipa, Baltazar, Fátima, Afonso, Julieta Alexandra Pereira
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/1822/78226
Resumo: 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.
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spelling In vivo anticancer activity of AZD3965: a systematic reviewCancerGlycolysisLactateMonocarboxylate transporter 1AZD3965In vivo modelsScience & TechnologyProliferating 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.This work has been funded by National funds, through the Foundation for Science and Technology (FCT)-project UIDB/50026/2020 and UIDP/50026/2020 and by the project NORTE-01- 0145-FEDER-000055, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). J.A. received a fellowship from FCT, ref. SFRH/BPD/116784/2016.Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoSilva, AnaAntunes, BeatrizBatista, AlbertaPinto-Ribeiro, FilipaBaltazar, FátimaAfonso, Julieta Alexandra Pereira20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/78226engSilva, A.; Antunes, B.; Batista, A.; Pinto-Ribeiro, F.; Baltazar, F.; Afonso, J. In Vivo Anticancer Activity of AZD3965: A Systematic Review. Molecules 2022, 27, 181. https://doi.org/10.3390/molecules270101811420-304910.3390/molecules2701018135011413181https://www.mdpi.com/1420-3049/27/1/181info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:44:22Zoai:repositorium.sdum.uminho.pt:1822/78226Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:42:02.144593Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv In vivo anticancer activity of AZD3965: a systematic review
title In vivo anticancer activity of AZD3965: a systematic review
spellingShingle In vivo anticancer activity of AZD3965: a systematic review
Silva, Ana
Cancer
Glycolysis
Lactate
Monocarboxylate transporter 1
AZD3965
In vivo models
Science & Technology
title_short 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_sort In vivo anticancer activity of AZD3965: a systematic review
author Silva, Ana
author_facet Silva, Ana
Antunes, Beatriz
Batista, Alberta
Pinto-Ribeiro, Filipa
Baltazar, Fátima
Afonso, Julieta Alexandra Pereira
author_role author
author2 Antunes, Beatriz
Batista, Alberta
Pinto-Ribeiro, Filipa
Baltazar, Fátima
Afonso, Julieta Alexandra Pereira
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Silva, Ana
Antunes, Beatriz
Batista, Alberta
Pinto-Ribeiro, Filipa
Baltazar, Fátima
Afonso, Julieta Alexandra Pereira
dc.subject.por.fl_str_mv Cancer
Glycolysis
Lactate
Monocarboxylate transporter 1
AZD3965
In vivo models
Science & Technology
topic Cancer
Glycolysis
Lactate
Monocarboxylate transporter 1
AZD3965
In vivo models
Science & Technology
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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/1822/78226
url https://hdl.handle.net/1822/78226
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Silva, A.; Antunes, B.; Batista, A.; Pinto-Ribeiro, F.; Baltazar, F.; Afonso, J. In Vivo Anticancer Activity of AZD3965: A Systematic Review. Molecules 2022, 27, 181. https://doi.org/10.3390/molecules27010181
1420-3049
10.3390/molecules27010181
35011413
181
https://www.mdpi.com/1420-3049/27/1/181
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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