Department of Respiratory Medicine' Juntendo University, Tokyo, Japan.
Department of Pathology, Juntendo University, Tokyo, Japan.
Thorac Cancer. 2021 Mar;12(5):715-719. doi: 10.1111/1759-7714.13829. Epub 2021 Jan 21.
To date, several studies have described the mechanism of resistance to first- or second-generation anaplastic lymphoma kinase (ALK) inhibitors. Secondary ALK mutations, ALK gene amplification, and other bypass signal activations (i.e., KRAS mutation, EGFR mutation, amplification of KIT, and increased autophosphorylation of EGFR) are known as resistance mechanisms. However, little has been previously reported on acquired resistance mechanisms to lorlatinib. Here, we report a case of a patient with ALK-positive lung adenocarcinoma that acquired resistance to lorlatinib during treatment for brain metastasis and showed histological transformation to squamous cell carcinoma with MET amplification. We also review the previous literature on the resistance mechanism to ALK inhibitors.
迄今为止，已有多项研究描述了第一代或第二代间变性淋巴瘤激酶 (ALK) 抑制剂耐药的机制。已知的耐药机制包括：ALK 继发性突变、ALK 基因扩增以及其他旁路信号激活（如 KRAS 突变、EGFR 突变、KIT 扩增和 EGFR 自身磷酸化增加）。然而，先前关于 lorlatinib 获得性耐药机制的报道较少。在此，我们报告了一例 ALK 阳性肺腺癌患者，该患者在治疗脑转移期间对 lorlatinib 产生耐药性，并出现伴有 MET 扩增的鳞状细胞癌组织学转化。我们还回顾了先前关于 ALK 抑制剂耐药机制的文献。
