HER2 amplification is an acquired resistance mechanism in ALK-rearranged non-small cell lung cancer. READ ARTICLE
Clinical Lung Cancer DOI: 10.1016/j.cllc.2021.06.012
Authors: David Chun Cheong Tsui, Dara Aisner, Hala Nijmeh, Liming Bao, Alexander Menter and Ross Camidge
Read MoreTargeted therapies lead to acquired resistance through multiple mechanisms. The selective pressure of newer, more potent TKIs results in new resistance mechanisms. Article gives overview of strategies for overcoming resistance to TKIs targeting the common oncogenic gene fusions in NSCLC. READ ARTICLE
Translational Lung Cancer Research DOI: 10.21037/tlcr-2019-cnsclc-06
Authors: Alessandro Russo, Andrés F. Cardona, Christian Caglevic, Paolo Manca, Alejandro Ruiz-Patiño, Oscar Arrieta, Christian Rolfo
Read MoreSpecific tyrosine-kinase inhibitors (TKIs) are widely used for the treatment of non-small-cell lung cancers with anaplastic lymphoma kinase (ALK) translocations. However, most treated patients eventually develop resistance to the TKIs. The histological transformation into small cell carcinoma is well known to be the underlying mechanism for acquired resistance; however, transformation to squamous cell carcinoma is extremely rare. We, herein, report a case of ALK rearrangement-positive adenocarcinoma that transformed to squamous cell carcinoma after administration of alectinib, and was found to be resistant to ceritinib. READ ARTICLE
OncoTargets and therapy DOI:10.2147/OTT.S236706
Authors: Kaiho T, Nakajima T, Iwasawa S, Yonemori Y, Yoshino I.
The development of targeted therapies has revolutionized the treatment of patients with lung cancer, especially non-small-cell lung cancer (NSCLC). Anaplastic lymphoma kinase (ALK) is a research hotspot of molecular targeted therapy for lung cancer. ALK tyrosine kinase inhibitors (TKIs) are highly effective for ALK-rearranged NSCLC-positive patients. These targeted therapies have significant clinical effects; however, they inevitably lead to acquired resistance. In previous studies, the histological transformation after ALK inhibitor treatment was mostly based on small-cell lung cancer (SCLC). The transformation from adenocarcinoma into squamous cell carcinoma in NSCLC after treatment with ALK TKI was extremely rare. This study aimed to report a case of lung cancer with a histological transformation from adenocarcinoma into squamous cell carcinoma after crizotinib treatment, still having the original ALK rearrangement at the molecular level. READ ARTICLE
Lung Cancer DOI:10.1016/j.lungcan.2020.01.001
Authors: Fenfang Wang, Jing Qin, Fajun Xie, Qihuan Wu, Hongyang Lu
Clinical benefit of ALK tyrosine kinase inhibitors (ALK-TKIs) in ALK-rearranged lung cancer has been limited by the inevitable development of acquired resistance, and bypass-molecular resistance mechanisms remain poorly understood. We investigated a novel therapeutic target through screening FDA-approved drugs in ALK-TKI-resistant models. Cerivastatin, the rate-limiting enzyme inhibitor of the mevalonate pathway, showed anti-cancer activity against ALK-TKI resistance in vitro/in vivo, accompanied by cytoplasmic retention and subsequent inactivation of transcriptional co-regulator YAP. The marked induction of YAP-targeted oncogenes (EGFR, AXL, CYR61, and TGFβR2) in resistant cells was abolished by cerivastatin. YAP silencing suppressed tumor growth in resistant cells, patient-derived xenografts, and EML4-ALK transgenic mice, whereas YAP overexpression decreased the responsiveness of parental cells to ALK inhibitor. In matched patient samples before/after ALK inhibitor treatment, nuclear..... READ ARTICLE
EMBO Molecular Medicine DOI:10.15252/emmm.201910581
Authors: Mi Ran Yun, Hun Mi Choi, You Won Lee, Hyeong Seok Joo, Chae Won Park, Jae Woo Choi, Dong Hwi Kim, Han Na Kang, Kyoung-Ho Pyo, Eun Joo Shin, Hyo Sup Shim, Ross A Soo, James Chih-Hsin Yang, Sung Sook Lee, Hyun Chang, Min Hwan Kim, Min Hee Hong, Hye Ryun Kim, Byoung Chul Cho
