title: Lung adenocarcinoma harboring concomitant SPTBN1-ALK fusion, c-Met overexpression, and HER-2 amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy.
abstract: Crizotinib is a multi-targeted tyrosine kinase inhibitor (TKI) with activity against mesenchymal-epithelial transition factor (MET) and anaplastic lymphoma kinase (ALK). However, the concomitant oncogenic drivers may affect the sensitivity of crizotinib. Herein, we present a 69-year-old never-smoker Chinese male with advanced lung adenocarcinoma harboring concomitant spectrin beta non-erythrocytic 1 (SPTBN1)-ALK fusion, c-Met overexpression, and human epidermal growth factor receptor-2 (HER-2) amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy. Although the patient received timely and comprehensive treatment, the overall survival was only 8 months. Therefore, c-Met overexpression, HER-2 gene amplification, and SPTBN1-ALK gene fusion can coexist in lung adenocarcinoma and may become a potential biomarker of cancer refractory to crizotinib, chemotherapy, and radiotherapy as well as of a relatively poor prognosis. In addition, the novel SPTBN1-ALK fusion gene may become a potential target for anti-tumor therapy.
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Fei-Fei
authors: FF
authors: Gu
authors: Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan University, Wuhan, China.
authors: Yong
authors: Y
authors: Zhang
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Yang-Yang
authors: YY
authors: Liu
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Xiao-Hua
authors: XH
authors: Hong
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Jin-Yan
authors: JY
authors: Liang
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Fan
authors: F
authors: Tong
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Jing-Song
authors: JS
authors: Yang
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. liulist2013@163.com.
authors: Li
authors: L
authors: Liu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D044466:Asian People; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D017809:Fatal Outcome; D005784:Gene Amplification; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D008297:Male; D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D011720:Pyrazoles; D011725:Pyridines; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011993:Recombinant Fusion Proteins; D013049:Spectrin / Q000235:genetics
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D000077547:Crizotinib; D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met; D011720:Pyrazoles; D011725:Pyridines; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D013049:Spectrin; C452439:SPTBN1 protein, human; C000626173:ALK protein, human; C508053:ERBB2 protein, human; C491743:MET protein, human
keywords: Chemotherapy; Crizotinib; HER-2; Lung adenocarcinoma; NSCLC; Oncogenic drivers; Radiotherapy; SPTBN1-ALK; c-Met