Immune Checkpoint Inhibitors in Melanoma: Review and Update
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Outros Autores: | |
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. |
id |
RCAP_766cf3020414cb9aec2abf114e33f6f1 |
---|---|
oai_identifier_str |
oai:ojs.revista.spdv.com.pt:article/970 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
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 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 |
|
_version_ |
1799130567472578560 |