Cargando…

The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer

The treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The dis...

Descripción completa

Detalles Bibliográficos
Autores principales: Gristina, Valerio, La Mantia, Maria, Iacono, Federica, Galvano, Antonio, Russo, Antonio, Bazan, Viviana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766858/
https://www.ncbi.nlm.nih.gov/pubmed/33352844
http://dx.doi.org/10.3390/ph13120474
_version_ 1783628819343605760
author Gristina, Valerio
La Mantia, Maria
Iacono, Federica
Galvano, Antonio
Russo, Antonio
Bazan, Viviana
author_facet Gristina, Valerio
La Mantia, Maria
Iacono, Federica
Galvano, Antonio
Russo, Antonio
Bazan, Viviana
author_sort Gristina, Valerio
collection PubMed
description The treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research. Unfortunately, acquired resistances regularly develop, hence disease progression occurs. Afterward, modern tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, and lorlatinib, have been approved by the Food and Drug Administration (FDA) for the management of anaplastic lymphoma kinase (ALK)-positive NSCLCs. Several compounds are currently under investigation to achieve the optimal strategy of therapy. Additionally, the results of ongoing clinical trials with novel-generation TKI will provide more evidence on the best sequence in the treatment of ALK-positive NSCLC patients. In this review, we provide a comprehensive overview of the state-of-the-art targeted therapy options in ALK-positive NSCLCs. Resistance, potential therapeutic strategies to overcome drug resistance, and future perspectives for this subset of patients are critically analyzed and summarized.
format Online
Article
Text
id pubmed-7766858
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-77668582020-12-28 The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer Gristina, Valerio La Mantia, Maria Iacono, Federica Galvano, Antonio Russo, Antonio Bazan, Viviana Pharmaceuticals (Basel) Review The treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research. Unfortunately, acquired resistances regularly develop, hence disease progression occurs. Afterward, modern tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, and lorlatinib, have been approved by the Food and Drug Administration (FDA) for the management of anaplastic lymphoma kinase (ALK)-positive NSCLCs. Several compounds are currently under investigation to achieve the optimal strategy of therapy. Additionally, the results of ongoing clinical trials with novel-generation TKI will provide more evidence on the best sequence in the treatment of ALK-positive NSCLC patients. In this review, we provide a comprehensive overview of the state-of-the-art targeted therapy options in ALK-positive NSCLCs. Resistance, potential therapeutic strategies to overcome drug resistance, and future perspectives for this subset of patients are critically analyzed and summarized. MDPI 2020-12-18 /pmc/articles/PMC7766858/ /pubmed/33352844 http://dx.doi.org/10.3390/ph13120474 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gristina, Valerio
La Mantia, Maria
Iacono, Federica
Galvano, Antonio
Russo, Antonio
Bazan, Viviana
The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer
title The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer
title_full The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer
title_fullStr The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer
title_full_unstemmed The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer
title_short The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer
title_sort emerging therapeutic landscape of alk inhibitors in non-small cell lung cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766858/
https://www.ncbi.nlm.nih.gov/pubmed/33352844
http://dx.doi.org/10.3390/ph13120474
work_keys_str_mv AT gristinavalerio theemergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT lamantiamaria theemergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT iaconofederica theemergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT galvanoantonio theemergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT russoantonio theemergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT bazanviviana theemergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT gristinavalerio emergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT lamantiamaria emergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT iaconofederica emergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT galvanoantonio emergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT russoantonio emergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer
AT bazanviviana emergingtherapeuticlandscapeofalkinhibitorsinnonsmallcelllungcancer