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Recent advances in targeted small‐molecule inhibitor therapy for non–small‐cell lung cancer—An update
Author(s) -
Atal Shubham,
Asokan Pravin,
Jhaj Ratinder
Publication year - 2020
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.13121
Subject(s) - osimertinib , afatinib , crizotinib , t790m , erlotinib , gefitinib , medicine , anaplastic lymphoma kinase , cancer research , lung cancer , ceritinib , egfr inhibitors , alectinib , epidermal growth factor receptor , cancer , oncology , malignant pleural effusion
What is known and objective Targeted small molecule EGFR Tyrosine Kinase Inhibitors (TKI's) and the Anaplastic Lymphoma Kinase (ALK) inhibitors have been promising tools for advanced non–small‐cell lung cancers (NSCLCs). However, tumours tend to develop subsequent mutations, rendering them drug‐resistant. Hence, alternative pathways of therapy need to be explored. Comment Gefitinib, erlotinib and afatinib, once considered as alternatives to platinum‐based cytotoxic chemotherapy, have been rendered ineffective in patients with NSCLCs harbouring T790M mutation. Osimertinib is effective in T790M‐mutant cancers, but not against those exhibiting the subsequent C797S mutation. ALK gene alterations have rendered tumours insensitive to crizotinib. However, lorlatinib and brigatinib are effective in tumours showing ALK+ mutations. Drugs acting through alternative pathways like the PD‐1 pathway, BRAF, VEGFR, EGFR antibodies and NTRK inhibition have been showing promising results. What is new and conclusions Osimertinib, brigatinib and allosteric C797S EGFR inhibitors like AI1045, BRAF inhibitors like LXH254 under trials and entrictinib, a recently approved NTRK inhibitor, have all shown improved progression‐free survival compared with earlier generations of small molecule inhibitors for NSCLCs.