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Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review

Neuroendocrine neoplasms (NENs) are rare malignancies arising most commonly in the gastrointestinal and bronchopulmonary systems. Neuroendocrine carcinomas (NECs) are a subgroup of NENs characterised by aggressive tumour biology, poor differentiation and dismal prognosis. Most NEC primary lesions ar...

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Autores principales: Robinson, Matthew D., Livesey, Daniel, Hubner, Richard A., Valle, Juan W., McNamara, Mairéad G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9983111/
https://www.ncbi.nlm.nih.gov/pubmed/36872945
http://dx.doi.org/10.1177/17588359231156870
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author Robinson, Matthew D.
Livesey, Daniel
Hubner, Richard A.
Valle, Juan W.
McNamara, Mairéad G.
author_facet Robinson, Matthew D.
Livesey, Daniel
Hubner, Richard A.
Valle, Juan W.
McNamara, Mairéad G.
author_sort Robinson, Matthew D.
collection PubMed
description Neuroendocrine neoplasms (NENs) are rare malignancies arising most commonly in the gastrointestinal and bronchopulmonary systems. Neuroendocrine carcinomas (NECs) are a subgroup of NENs characterised by aggressive tumour biology, poor differentiation and dismal prognosis. Most NEC primary lesions arise in the pulmonary system. However, a small proportion arise outside of the lung and are termed extrapulmonary (EP)-, poorly differentiated (PD)-NECs. Patients with local or locoregional disease may benefit from surgical excision; however, this is often not an option, due to late presentation. To date, treatment has mirrored that of small-cell lung cancer, with platinum–etoposide forming the basis of first-line treatment. There is a lack of consensus in relation to the most effective second-line treatment option. Low incidence, an absence of representative preclinical models and a lack of understanding of the tumour microenvironment all present challenges to drug development in this disease group. However, progress made in elucidating the mutational landscape of EP-PD-NEC and the observations made in several clinical trials are paving the way towards improving outcomes for these patients. The optimisation and strategic delivery of chemotherapeutic interventions according to tumour characteristics and the utilisation of targeted and immune therapies in clinical studies have yielded mixed results. Targeted therapies that complement specific genetic aberrations are under investigation, including AURKA inhibitors in those with MYCN amplifications, BRAF inhibitors in those with BRAFV600E mutations and EGFR suppression, and Ataxia Telangiectasia and Rad3-related inhibitors in patients with ATM mutations. Immune checkpoint inhibitors (ICIs) have conferred promising results in several clinical trials, particularly with dual ICIs and in combination with targeted therapy or chemotherapy. However, further prospective investigations are required to elucidate the impact of programmed cell death ligand 1 expression, tumour mutational burden and microsatellite instability on response. This review aims to explore the most recent developments in the treatment of EP-PD-NEC and contribute towards the requirement for clinical guidance founded on prospective evidence.
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spelling pubmed-99831112023-03-04 Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review Robinson, Matthew D. Livesey, Daniel Hubner, Richard A. Valle, Juan W. McNamara, Mairéad G. Ther Adv Med Oncol Advances in Diagnosis and Treatment of Neuroendocrine Neoplasms Neuroendocrine neoplasms (NENs) are rare malignancies arising most commonly in the gastrointestinal and bronchopulmonary systems. Neuroendocrine carcinomas (NECs) are a subgroup of NENs characterised by aggressive tumour biology, poor differentiation and dismal prognosis. Most NEC primary lesions arise in the pulmonary system. However, a small proportion arise outside of the lung and are termed extrapulmonary (EP)-, poorly differentiated (PD)-NECs. Patients with local or locoregional disease may benefit from surgical excision; however, this is often not an option, due to late presentation. To date, treatment has mirrored that of small-cell lung cancer, with platinum–etoposide forming the basis of first-line treatment. There is a lack of consensus in relation to the most effective second-line treatment option. Low incidence, an absence of representative preclinical models and a lack of understanding of the tumour microenvironment all present challenges to drug development in this disease group. However, progress made in elucidating the mutational landscape of EP-PD-NEC and the observations made in several clinical trials are paving the way towards improving outcomes for these patients. The optimisation and strategic delivery of chemotherapeutic interventions according to tumour characteristics and the utilisation of targeted and immune therapies in clinical studies have yielded mixed results. Targeted therapies that complement specific genetic aberrations are under investigation, including AURKA inhibitors in those with MYCN amplifications, BRAF inhibitors in those with BRAFV600E mutations and EGFR suppression, and Ataxia Telangiectasia and Rad3-related inhibitors in patients with ATM mutations. Immune checkpoint inhibitors (ICIs) have conferred promising results in several clinical trials, particularly with dual ICIs and in combination with targeted therapy or chemotherapy. However, further prospective investigations are required to elucidate the impact of programmed cell death ligand 1 expression, tumour mutational burden and microsatellite instability on response. This review aims to explore the most recent developments in the treatment of EP-PD-NEC and contribute towards the requirement for clinical guidance founded on prospective evidence. SAGE Publications 2023-03-01 /pmc/articles/PMC9983111/ /pubmed/36872945 http://dx.doi.org/10.1177/17588359231156870 Text en © The Author(s), 2023 https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Advances in Diagnosis and Treatment of Neuroendocrine Neoplasms
Robinson, Matthew D.
Livesey, Daniel
Hubner, Richard A.
Valle, Juan W.
McNamara, Mairéad G.
Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review
title Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review
title_full Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review
title_fullStr Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review
title_full_unstemmed Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review
title_short Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review
title_sort future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review
topic Advances in Diagnosis and Treatment of Neuroendocrine Neoplasms
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9983111/
https://www.ncbi.nlm.nih.gov/pubmed/36872945
http://dx.doi.org/10.1177/17588359231156870
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