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

Authors
  • Gristina, Valerio1
  • La Mantia, Maria1
  • Iacono, Federica1
  • Galvano, Antonio1
  • Russo, Antonio1
  • Bazan, Viviana2
  • 1 (A.R.)
  • 2 Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy
Type
Published Article
Journal
Pharmaceuticals
Publisher
MDPI AG
Publication Date
Dec 18, 2020
Volume
13
Issue
12
Identifiers
DOI: 10.3390/ph13120474
PMID: 33352844
PMCID: PMC7766858
Source
PubMed Central
Keywords
Disciplines
  • Review
License
Green

Abstract

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.

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