Makuuchi Yosuke, Hayashi Hidetoshi, Haratani Koji, Tanizaki Junko, Tanaka Kaoru, Takeda Masayuki, Sakai Kazuko, Shimizu Shigeki, Ito Akihiko, Nishio Kazuto, Nakagawa Kazuhiko
Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
Department of Hematology, Graduate School of Medicine, Osaka City University, Abeno, Osaka 545-8585, Japan.
Oncotarget. 2018 May 1;9(33):23315-23319. doi: 10.18632/oncotarget.25143.
The second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) alectinib and ceritinib are standard treatment options for patients with non-small cell lung cancer (NSCLC) positive for fusion genes. However, almost all patients eventually develop resistance to these drugs. We here report a case of -rearranged NSCLC that developed resistance to alectinib but remained sensitive to ceritinib. The L1196M mutation within the fusion gene was detected after failure of consecutive treatment with crizotinib and alectinib, but no other mechanism underlying acquired resistance to ALK-TKIs was found to be operative. Given the increasing application of ALK-TKIs to the treatment of patients with -rearranged NSCLC, further clinical evaluation is warranted to provide a better understanding of the mechanisms of acquired resistance to these agents and to inform treatment strategies for such tumors harboring secondary mutations.
第二代间变性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂（TKIs）阿来替尼和色瑞替尼是 融合基因阳性的非小细胞肺癌（NSCLC）患者的标准治疗选择。然而，几乎所有患者最终都会对这些药物产生耐药性。我们在此报告一例 重排的NSCLC患者，该患者对阿来替尼产生耐药，但对色瑞替尼仍敏感。在克唑替尼和阿来替尼连续治疗失败后，检测到 融合基因内的L1196M突变，但未发现其他导致对ALK-TKIs获得性耐药的机制。鉴于ALK-TKIs在 重排的NSCLC患者治疗中的应用日益增加，有必要进行进一步的临床评估，以更好地了解对这些药物获得性耐药的机制，并为携带继发性突变的此类肿瘤提供治疗策略。
