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. 2020 Jun;45(3):580-584.
doi: 10.1111/jcpt.13121. Epub 2020 Feb 18.

Recent advances in targeted small-molecule inhibitor therapy for non-small-cell lung cancer-An update

Shubham Atal  1 , Pravin Asokan  1 , Ratinder Jhaj  1
Affiliations

Recent advances in targeted small-molecule inhibitor therapy for non-small-cell lung cancer-An update

Shubham Atal et al. J Clin Pharm Ther. 2020 Jun.

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.

Keywords: ALK inhibitor; EGFR inhibitor; NSCLC; resistant cancer; targeted therapy.

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References

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