Recent advances in targeted small‐molecule inhibitor therapy for non–small‐cell lung cancer—An update. (18th February 2020)

• Record Type: Journal Article
• Authors: Atal, Shubham; Asokan, Pravin; Jhaj, Ratinder
• Is Part Of: Journal of clinical pharmacy and therapeutics. Volume 45:Number 3(2020)
• Page Start: 580
• Page End: 584
• Publication Date: 2020-02-18
• Subjects: ALK inhibitor -- EGFR inhibitor -- NSCLC -- resistant cancer -- targeted therapy; Clinical pharmacology -- Periodicals; Chemotherapy -- Periodicals; 615
• DOI: 10.1111/jcpt.13121
• Languages: English
• ISSNs: 0269-4727

Abstract

Abstract: 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.