In vivo anticancer activity of AZD3965: a systematic review
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , |
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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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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
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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1799132971577376768 |