Dramatic response to alectinib in a lung cancer patient with a novel VKORC1L1-ALK fusion and an acquired ALK T1151K mutation

ALK-rearranged lung cancer defines a distinctive molecular cohort of patients whose
outcomes are significantly improved by the availability of ALK inhibitors. Thus, it is imperative
for clinicians to screen appropriate patients for this driver mutation with a molecular testing
platform capable of capturing all ALK fusions. Here, we report a novel VKORC1L1-ALK fusion
and an ALK T1151K resistance mutation detected in a lung cancer patient who had been on
crizotinib for over 8 years. Alectinib induced a dramatic response in this patient demonstrating
its clinical activity against T1151K. This case illustrates the importance of performing repeat
biopsy to explore mechanism(s) of resistance when patients experience disease progression
on an ALK inhibitor. The approach has a direct therapeutic impact particularly when an ALK
resistance mutation is identified. READ ARTICLE

Lung Cancer: Targets and Therapy
DOI:10.2147/LCTT.S186804

Authors: Viola W Zhu, Alexa B Schrock, Thangavijayan Bosemani, Bryan S Benn, Siraj M Ali, and Sai-Hong Ignatius Ou

Case Study, group2Kirk SmithNovember 29, 2021VKORC1L1, T1151, fusion, resistance, crizotinib, lorlatinib

Sensitivity of eight types of ALK fusion variant to alectinib in ALK-transformed cells

Tyrosine kinase inhibitors of anaplastic lymphoma kinase (ALK-TKIs) including alectinib have been the standard therapy against ALK fusion gene-positive non-small cell lung cancers (NSCLCs). Many ALK fusion variants have been identified in NSCLCs, and the predominant variants are echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) variant 1 (V1), V2 and V3a/b. However, there have been conflicting reports on the clinical responses of these variants to ALK-TKIs, and there are few reports on other less common ALK variants. To examine the influence of ALK variants on the efficacy of ALK-TKIs, we analyzed the sensitivity to alectinib of eight types of ALK variant: three major variants (V1, V2 and V3a) and five less common variants (V4; kinesin family member 5-ALK; kinesin light chain 1-ALK; striatin, calmodulin-binding protein-ALK; and tropomyosin-receptor kinase fused gene-ALK). Analysis was done by cell-free kinase assays using the recombinant proteins and by cell, growth assay..... READ ARTICLE

Anticancer Drugs DOI:10.1097/CAD.0000000000001249

Authors: Furugaki K, Harada N, Yoshimura Y.

Pre-Clinical, group3Kirk SmithSeptember 13, 2021alectinib, ALK, EML4, fusion, KIF5B, KLC1, lung cancer, STRN, TFG, variant