Immune Checkpoint Inhibitors in Melanoma: Review and Update

Detalhes bibliográficos
Autor(a) principal: Matos Pires, Eugénia
Data de Publicação: 2018
Outros Autores: Moura, Cecília
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://doi.org/10.29021/spdv.76.3.970
Resumo: The overall increasing incidence of melanoma will very probably be the trend over the next two decades. This data stresses the need for new therapeutic resources, other than classic chemotherapy. Nevertheless, the treatment of advanced melanoma has been changed in the last decade due to novel therapeutic strategies, including immunotherapy with immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Inhibition of these targets enhances immune host response against cancer and results in durable objective responses, establishing immunotherapy as standard treatment for BRAF wild-type melanoma patients in advanced stages (III – unresectable and IV – metastases at distant sites). Anti-CTLA-4, ipilimumab, was the first–in-class immune checkpoint inhibitor to show improvement in overall survival in advanced melanoma. Latter, anti-PD-1 agents, nivolumab and pembrolizumab, have improved tumour response and tolerability in comparison with ipilimumab. Differences in outcome are expected considering the distinct target of checkpoint inhibition pathways. In this setting, it is of utmost importance the assessment of efficacy by combined therapy and the identification of biomarkers capable of predicting response to anti-CTLA-4 and anti-PD-1. After a previous review on cancer biology and mechanisms of action of immune checkpoint inhibitors we will focus on the main data on the immune checkpoint inhibitors for melanoma currently available in daily practice.
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spelling Immune Checkpoint Inhibitors in Melanoma: Review and UpdateRevisão e Atualização dos Inibidores dos Checkpoints Immunológicos no MelanomaAntibodiesMonoclonalCell Cycle CheckpointsCTLA-4 AntigenImmunotherapyIpilimumabMelanomaNivolumabProgrammed Cell Death 1 ReceptorAnticorpos MonoclonaisAntígeno CTLA-4ImunoterapiaIpilimumabMelanomaNivolumabPembrolizumabPontos de Controlo do Ciclo CelularReceptor de Morte Celular Programada 1The overall increasing incidence of melanoma will very probably be the trend over the next two decades. This data stresses the need for new therapeutic resources, other than classic chemotherapy. Nevertheless, the treatment of advanced melanoma has been changed in the last decade due to novel therapeutic strategies, including immunotherapy with immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Inhibition of these targets enhances immune host response against cancer and results in durable objective responses, establishing immunotherapy as standard treatment for BRAF wild-type melanoma patients in advanced stages (III – unresectable and IV – metastases at distant sites). Anti-CTLA-4, ipilimumab, was the first–in-class immune checkpoint inhibitor to show improvement in overall survival in advanced melanoma. Latter, anti-PD-1 agents, nivolumab and pembrolizumab, have improved tumour response and tolerability in comparison with ipilimumab. Differences in outcome are expected considering the distinct target of checkpoint inhibition pathways. In this setting, it is of utmost importance the assessment of efficacy by combined therapy and the identification of biomarkers capable of predicting response to anti-CTLA-4 and anti-PD-1. After a previous review on cancer biology and mechanisms of action of immune checkpoint inhibitors we will focus on the main data on the immune checkpoint inhibitors for melanoma currently available in daily practice.A incidência do melanoma está a aumentar de uma forma global e essa tendência manter-se-á muito provavelmente nas próximas duas décadas. Estes dados reforçam a necessidade de novos alvos terapêuticos, em alternativa à quimioterapia clássica para o tratamento do melanoma avançado. Com efeito, ao longo da última década, os novos conhecimentos relativos à biologia tumoral revolucionaram a terapêutica do melanoma, incluindo a imunoterapia com os inibidores dos “checkpoints” imunológicos, cujos alvos terapêuticos são as proteínas CTLA-4 (cytotoxic T lymphocyte-associated protein 4) e PD-1 (programmed cell death protein 1). A inibição destes alvos permite a modulação da resposta imune do hospedeiro contra o desenvolvimento tumoral, com respostas objetivas sustentadas no controlo da doença. Face a estes resultados, a imunoterapia tornou-se o tratamento de referência nos doentes com melanoma avançado (estadio III irressecável ou estadio IV, com metástases à distância), sem mutação BRAF identificada. O ipilimumab (anti CTLA-4) foi o primeiro “checkpoint” imunológico inibitório a demonstrar aumento na sobrevida global no tratamento do melanoma avançado. Mais tarde, o nivolumab e o pembrolizumab (ambos anti-PD-1) evidenciaram melhores resultados em termos de sobrevida global e tolerabilidade do que o ipilimumab. Estes resultados são expectáveis, na medida em que as vias de inibição dos “checkpoints” imunológicos são diferentes. Neste contexto, impõe-se a avaliação da eficácia da terapêutica combinada e a identificação de biomarcadores que possibilitem a previsão de resposta aos anti-CTLA-4 e anti-PD-1. Após um trabalho prévio em que foram sumariamente revistos os mecanismos de desenvolvimento tumoral e de ação dos “checkpoints” imunológicos inibitórios, propomo-nos efetuar uma revisão sobre os inibidores dos “checkpoints” imunológicos, atualmente disponíveis na prática clínica para o tratamento do melanoma avançado.Sociedade Portuguesa de Dermatologia e Venereologia2018-10-05T00:00:00Zjournal articleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.29021/spdv.76.3.970oai:ojs.revista.spdv.com.pt:article/970Journal of the Portuguese Society of Dermatology and Venereology; Vol 76 No 3 (2018): July - September; 237-252Revista da Sociedade Portuguesa de Dermatologia e Venereologia; v. 76 n. 3 (2018): Julho - Setembro; 237-2522182-24092182-2395reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAPenghttps://revista.spdv.com.pt/index.php/spdv/article/view/970https://doi.org/10.29021/spdv.76.3.970https://revista.spdv.com.pt/index.php/spdv/article/view/970/579Matos Pires, EugéniaMoura, Cecíliainfo:eu-repo/semantics/openAccess2022-10-06T12:35:09Zoai:ojs.revista.spdv.com.pt:article/970Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:08.146543Repositório 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 Immune Checkpoint Inhibitors in Melanoma: Review and Update
Revisão e Atualização dos Inibidores dos Checkpoints Immunológicos no Melanoma
title Immune Checkpoint Inhibitors in Melanoma: Review and Update
spellingShingle Immune Checkpoint Inhibitors in Melanoma: Review and Update
Matos Pires, Eugénia
Antibodies
Monoclonal
Cell Cycle Checkpoints
CTLA-4 Antigen
Immunotherapy
Ipilimumab
Melanoma
Nivolumab
Programmed Cell Death 1 Receptor
Anticorpos Monoclonais
Antígeno CTLA-4
Imunoterapia
Ipilimumab
Melanoma
Nivolumab
Pembrolizumab
Pontos de Controlo do Ciclo Celular
Receptor de Morte Celular Programada 1
title_short Immune Checkpoint Inhibitors in Melanoma: Review and Update
title_full Immune Checkpoint Inhibitors in Melanoma: Review and Update
title_fullStr Immune Checkpoint Inhibitors in Melanoma: Review and Update
title_full_unstemmed Immune Checkpoint Inhibitors in Melanoma: Review and Update
title_sort Immune Checkpoint Inhibitors in Melanoma: Review and Update
author Matos Pires, Eugénia
author_facet Matos Pires, Eugénia
Moura, Cecília
author_role author
author2 Moura, Cecília
author2_role author
dc.contributor.author.fl_str_mv Matos Pires, Eugénia
Moura, Cecília
dc.subject.por.fl_str_mv Antibodies
Monoclonal
Cell Cycle Checkpoints
CTLA-4 Antigen
Immunotherapy
Ipilimumab
Melanoma
Nivolumab
Programmed Cell Death 1 Receptor
Anticorpos Monoclonais
Antígeno CTLA-4
Imunoterapia
Ipilimumab
Melanoma
Nivolumab
Pembrolizumab
Pontos de Controlo do Ciclo Celular
Receptor de Morte Celular Programada 1
topic Antibodies
Monoclonal
Cell Cycle Checkpoints
CTLA-4 Antigen
Immunotherapy
Ipilimumab
Melanoma
Nivolumab
Programmed Cell Death 1 Receptor
Anticorpos Monoclonais
Antígeno CTLA-4
Imunoterapia
Ipilimumab
Melanoma
Nivolumab
Pembrolizumab
Pontos de Controlo do Ciclo Celular
Receptor de Morte Celular Programada 1
description The overall increasing incidence of melanoma will very probably be the trend over the next two decades. This data stresses the need for new therapeutic resources, other than classic chemotherapy. Nevertheless, the treatment of advanced melanoma has been changed in the last decade due to novel therapeutic strategies, including immunotherapy with immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Inhibition of these targets enhances immune host response against cancer and results in durable objective responses, establishing immunotherapy as standard treatment for BRAF wild-type melanoma patients in advanced stages (III – unresectable and IV – metastases at distant sites). Anti-CTLA-4, ipilimumab, was the first–in-class immune checkpoint inhibitor to show improvement in overall survival in advanced melanoma. Latter, anti-PD-1 agents, nivolumab and pembrolizumab, have improved tumour response and tolerability in comparison with ipilimumab. Differences in outcome are expected considering the distinct target of checkpoint inhibition pathways. In this setting, it is of utmost importance the assessment of efficacy by combined therapy and the identification of biomarkers capable of predicting response to anti-CTLA-4 and anti-PD-1. After a previous review on cancer biology and mechanisms of action of immune checkpoint inhibitors we will focus on the main data on the immune checkpoint inhibitors for melanoma currently available in daily practice.
publishDate 2018
dc.date.none.fl_str_mv 2018-10-05T00:00:00Z
dc.type.driver.fl_str_mv journal article
info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://doi.org/10.29021/spdv.76.3.970
oai:ojs.revista.spdv.com.pt:article/970
url https://doi.org/10.29021/spdv.76.3.970
identifier_str_mv oai:ojs.revista.spdv.com.pt:article/970
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://revista.spdv.com.pt/index.php/spdv/article/view/970
https://doi.org/10.29021/spdv.76.3.970
https://revista.spdv.com.pt/index.php/spdv/article/view/970/579
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 Sociedade Portuguesa de Dermatologia e Venereologia
publisher.none.fl_str_mv Sociedade Portuguesa de Dermatologia e Venereologia
dc.source.none.fl_str_mv Journal of the Portuguese Society of Dermatology and Venereology; Vol 76 No 3 (2018): July - September; 237-252
Revista da Sociedade Portuguesa de Dermatologia e Venereologia; v. 76 n. 3 (2018): Julho - Setembro; 237-252
2182-2409
2182-2395
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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)
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