Abstract
Anaplastic lymphoma kinase (ALK) rearrangements were first implicated as driving mutations in non-small cell lung cancer in 2007. Since then, a number of novel, small-molecule inhibitors directed against the ALK receptor have demonstrated superiority over standard chemotherapies in the treatment of ALK rearrangement-positive lung cancer. Of considerable importance when considering such therapies is the ability of each to overcome mutations conferring acquired resistance, as well as penetrate the central nervous system (CNS), the most common site of metastasis and traditionally the most difficult to breach. Herein is a review of the efficacy, indications, and degree of CNS penetration for the ALK-targeting agents crizotinib, ceretinib, alectinib, brigatinib, and lorlatinib, as well as a summary of ongoing clinical trials comparing these drugs.
Keywords:
ALK rearrangement; NSCLC; alectinib; brigatinib; ceritinib; crizotinib; lorlatinib; review.
Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
MeSH terms
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Aminopyridines
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Anaplastic Lymphoma Kinase
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Carbazoles / pharmacology
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Carbazoles / therapeutic use
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / genetics
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Clinical Trials as Topic
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Crizotinib
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Drug Resistance, Neoplasm / drug effects
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Humans
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Lactams
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Lactams, Macrocyclic / pharmacology
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Lactams, Macrocyclic / therapeutic use
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / genetics
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Mutation
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Organophosphorus Compounds / pharmacology
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Organophosphorus Compounds / therapeutic use
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Piperidines / pharmacology
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Piperidines / therapeutic use
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Pyrazoles / pharmacology
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Pyrazoles / therapeutic use
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Pyridines / pharmacology
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Pyridines / therapeutic use
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Pyrimidines / pharmacology
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Pyrimidines / therapeutic use
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
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Receptor Protein-Tyrosine Kinases / genetics*
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Small Molecule Libraries / pharmacology
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Small Molecule Libraries / therapeutic use*
Substances
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Aminopyridines
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Antineoplastic Agents
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Carbazoles
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Lactams
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Lactams, Macrocyclic
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Organophosphorus Compounds
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Piperidines
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Pyrazoles
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Pyridines
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Pyrimidines
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Small Molecule Libraries
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Crizotinib
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ALK protein, human
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Anaplastic Lymphoma Kinase
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Receptor Protein-Tyrosine Kinases
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brigatinib
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alectinib
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lorlatinib