The ALK gene rearrangement is the second most common driver genomic alteration accounting for approximately 3% to 7% of patients with approved targeted therapies in NSCLC, after EGFR gene mutations. We here describe a rare case of a patient with STRN-ALK–rearranged NSCLC. READ ARTICLE
Journal of thoracic Oncology DOI: 10.1016/j.jtocrr.2020.100125
Authors: Misako Nagasaka, Nagaratna Sarvadevabatla, Shawn Iwata, Yubin Ge, Ammar Sukari, Christian Klosowski, Ronald Yanagihara
Read MoreHowever, the concurrent two ALK rearrangements within the same patient have rarely previously been reported. Here, we describe a novel CCNY-ALK (C1:A20) and ATIC-ALK (A7:A20), coexisting in the same case with poorly differentiated NSCLC and providing evidence of its sensitivity to ALK inhibitors. The newly identified rearrangement partners can be added to the list of ALK rearrangements that occurred in ALK-positive NSCLC, as it could lead to prolonged disease control. Also, while different ALK rearrangement variants might bring differing clinical outcomes, we discuss the impact of the co-mutations of these two ALK rearrangements on the sensitivity to ALK inhibitors. However, the impact of co-mutations on the pathogenesis of NSCLC should be further studied to supply more theoretical insight that co-mutations present for personalized anti-cancer therapy. READ ARTICLE
Translational Lung Cancer Research DOI: 10.21037/tlcr-20-1049
Authors: Xuan Wu, Hanqiong Zhou, Zhen He, Zhe Zhang, Wen Feng, Jiuzhou Zhao3, Haiyang Chen, Shuai Wang, Wei Wang, Qiming Wang
Read More... Herein we report a novel ALK fusion partner, the Linc00308/D21S2088E intergenic region, that conferred responsiveness to crizotinib in a patient with lung adenocarcinoma (LUAD)... Thus, we have provided proof that patients with advanced NSCLC harboring a Linc00308/D21S2088E intergenic region ALK may benefit from crizotinib, expanding the spectrum of ALK fusion variants to optimize treated strategy. READ ARTICLE
Journal of Thoracic Oncology DOI:10.1016/j.jtho.2020.03.009
Authors: Jian Zhang, Chang Zou, Chenzhi Zhou, Yifeng Luo, Qiong He, Yu Sun, Jianwen Zhou, Zunfu Ke
... Using RNA sequencing, we show a clear evolutionary path from drug-sensitive parental cells to drug-tolerant persisters and long-term derived drug-acquired resistant cells. We are currently profiling vulnerabilities of drug-tolerant EGFR-mutant and EML4-ALK fusion persisters using genetic and pharmacologic approaches. In conclusion, YAP activation is a functional marker of EGFR-mutant and EML4-ALK fusion persisters derived under high-dose drug treatment with third-generation TKIs. Targeting YAP activation either on the level of upstream signaling input, its relocalization between cytoplasm and nucleus, or its action as transcriptional coactivator may represent a promising combinatorial treatment approach to limit resistance development and improve patient survival in lung adenocarcinoma. READ ARTICLE
Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.12.070
Authors: F. Haderk, C. Fernández-Méndez, K. N. Shah, W. Wu, J. Guan, J. Rotow, D. Allegakoen, V. Olivas, S. Bandyopadhyay, C. Kuo, T. Bivona
... Here, we report a case of adenocarcinoma harboring a novel S1 RNA binding domain 1 (SRBD1)–ALK fusion gene identified accidentally during routine molecular profiling by next-generation sequencing... Without any other oncogenic mutation detected, we speculate that the novel SRBD1-ALK fusion served as a driver mutation of the patient’s disease. And ALK TKIs might be effective in the treatment of tumors with this new fusion gene. READ ARTICLE
Journal of Thoracic Oncology DOI:10.1016/j.jtho.2018.11.027
Authors: Xue Hou, Huamin Xu, Likun Chen
