title: Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib.
abstract: A 56-year-old woman, a never-smoker, had postoperative recurrence of anaplastic lymphoma kinase rearranged lung cancer. She achieved a partial response to treatment with an anaplastic lymphoma kinase tyrosine kinase inhibitor, crizotinib. After the tumor regrowth, crizotinib was switched to alectinib; once again a partial response was observed. At the second recurrence, transbronchial needle aspiration of the right paratracheal node was performed, which revealed cytological findings of small-cell carcinoma. While treatment with cisplatin-irinotecan chemotherapy made reduction of some tumor shadows, including the biopsied mediastinal lymph nodes, new, small, nodular shadows, highly suggestive of pulmonary metastases, were detected in both lung fields. This case may show proof of the transformation to small-cell lung cancer as a mechanism of resistance to anaplastic lymphoma kinase tyrosine kinase inhibitors in anaplastic lymphoma kinase rearranged tumor. However, this transformation may also be only one part of the resistance mechanism of the heterogeneous tumor.
authors.affiliation: Department of Medical Oncology, Japanese Red Cross Medical Center, Shibuya, Tokyo aaa17580@pop06.odn.ne.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Department of Respiratory Medicine, Japanese Red Cross Medical Center, Shibuya, Tokyo.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ikushima
authors.affiliation: Department of Respiratory Medicine, Japanese Red Cross Medical Center, Shibuya, Tokyo.
authors.forename: Ryu
authors.initials: R
authors.lastname: Ono
authors.affiliation: Department of Respiratory Medicine, Japanese Red Cross Medical Center, Shibuya, Tokyo.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Awano
authors.affiliation: Department of Respiratory Medicine, Japanese Red Cross Medical Center, Shibuya, Tokyo.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Thoracic Surgery, Japanese Red Cross Medical Center, Shibuya, Tokyo.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Furuhata
authors.affiliation: Department of Thoracic Surgery, Japanese Red Cross Medical Center, Shibuya, Tokyo.
authors.forename: Kento
authors.initials: K
authors.lastname: Fukumoto
authors.affiliation: Department of Pathology, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumasaka
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D055752:Small Cell Lung Carcinoma / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C582670:alectinib
keywords: ALK-positive lung cancer; acquired resistance; small-cell lung cancer; transformation