Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance
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: | http://hdl.handle.net/10316/103390 https://doi.org/10.3390/molecules27072201 |
Resumo: | Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literature. In this review, we discuss the development of proteasome inhibitors and the mechanisms of innate and acquired resistance to their activity-a major challenge in preclinical and clinical therapeutics. An improved understanding of these mechanisms is crucial to guiding the design of new and more effective drugs to tackle these devastating diseases. In addition, we provide a comprehensive overview of proteasome inhibitors used in combination with other chemotherapeutic agents, as this is a key strategy to combat resistance. |
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Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistanceubiquitin–proteasome pathwayproteasome inhibitorsmechanisms of resistanceinnate resistanceacquired resistancemultiple myelomacancerAdultBortezomibHumansProteasome Endopeptidase ComplexProteasome InhibitorsQuality of LifeAntineoplastic AgentsMultiple MyelomaNeoplasmsProteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literature. In this review, we discuss the development of proteasome inhibitors and the mechanisms of innate and acquired resistance to their activity-a major challenge in preclinical and clinical therapeutics. An improved understanding of these mechanisms is crucial to guiding the design of new and more effective drugs to tackle these devastating diseases. In addition, we provide a comprehensive overview of proteasome inhibitors used in combination with other chemotherapeutic agents, as this is a key strategy to combat resistance.MDPI2022-03-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/103390http://hdl.handle.net/10316/103390https://doi.org/10.3390/molecules27072201eng1420-3049Leonardo-Sousa, CarlotaCarvalho, Andreia NevesGuedes, Romina A.Fernandes, Pedro M. P.Aniceto, NatáliaSalvador, Jorge A. R.Gama, Maria JoãoGuedes, Rita C.info: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:RCAAP2022-11-11T21:39:35Zoai:estudogeral.uc.pt:10316/103390Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:20:14.266427Repositório 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 |
Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance |
title |
Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance |
spellingShingle |
Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance Leonardo-Sousa, Carlota ubiquitin–proteasome pathway proteasome inhibitors mechanisms of resistance innate resistance acquired resistance multiple myeloma cancer Adult Bortezomib Humans Proteasome Endopeptidase Complex Proteasome Inhibitors Quality of Life Antineoplastic Agents Multiple Myeloma Neoplasms |
title_short |
Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance |
title_full |
Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance |
title_fullStr |
Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance |
title_full_unstemmed |
Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance |
title_sort |
Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance |
author |
Leonardo-Sousa, Carlota |
author_facet |
Leonardo-Sousa, Carlota Carvalho, Andreia Neves Guedes, Romina A. Fernandes, Pedro M. P. Aniceto, Natália Salvador, Jorge A. R. Gama, Maria João Guedes, Rita C. |
author_role |
author |
author2 |
Carvalho, Andreia Neves Guedes, Romina A. Fernandes, Pedro M. P. Aniceto, Natália Salvador, Jorge A. R. Gama, Maria João Guedes, Rita C. |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Leonardo-Sousa, Carlota Carvalho, Andreia Neves Guedes, Romina A. Fernandes, Pedro M. P. Aniceto, Natália Salvador, Jorge A. R. Gama, Maria João Guedes, Rita C. |
dc.subject.por.fl_str_mv |
ubiquitin–proteasome pathway proteasome inhibitors mechanisms of resistance innate resistance acquired resistance multiple myeloma cancer Adult Bortezomib Humans Proteasome Endopeptidase Complex Proteasome Inhibitors Quality of Life Antineoplastic Agents Multiple Myeloma Neoplasms |
topic |
ubiquitin–proteasome pathway proteasome inhibitors mechanisms of resistance innate resistance acquired resistance multiple myeloma cancer Adult Bortezomib Humans Proteasome Endopeptidase Complex Proteasome Inhibitors Quality of Life Antineoplastic Agents Multiple Myeloma Neoplasms |
description |
Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literature. In this review, we discuss the development of proteasome inhibitors and the mechanisms of innate and acquired resistance to their activity-a major challenge in preclinical and clinical therapeutics. An improved understanding of these mechanisms is crucial to guiding the design of new and more effective drugs to tackle these devastating diseases. In addition, we provide a comprehensive overview of proteasome inhibitors used in combination with other chemotherapeutic agents, as this is a key strategy to combat resistance. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-03-28 |
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 |
http://hdl.handle.net/10316/103390 http://hdl.handle.net/10316/103390 https://doi.org/10.3390/molecules27072201 |
url |
http://hdl.handle.net/10316/103390 https://doi.org/10.3390/molecules27072201 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1420-3049 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
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 |
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 |
repository.mail.fl_str_mv |
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1817550311140622336 |