Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo, Japan; Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
Cancer Sci. 2013 Nov;104(11):1396-400. doi: 10.1111/cas.12275. Epub 2013 Oct 1.
Development of lung adenocarcinoma (LADC), the most frequent histological type of lung cancer, depends in many cases on the activation of "driver" oncogenes such as KRAS, epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK). Inhibitors that target the EGFR and ALK tyrosine kinases show therapeutic effects against LADCs containing EGFR gene mutations and ALK gene fusions, respectively. Recently, we and others identified the RET fusion gene as a new targetable driver gene in LADC. The RET fusions occur in 1-2% of LADCs. Existing US Food and Drug Administration-approved inhibitors of RET tyrosine kinase show promising therapeutic effects both in vitro and in vivo, as well as in a few patients. Clinical trials are underway to investigate the therapeutic effects of RET tyrosine kinase inhibitors, such as vandetanib (ZD6474) and cabozantinib (XL184), in patients with RET fusion-positive non-small-cell lung cancer.
肺腺癌（LADC）的发生和发展，最常见的肺癌组织学类型，在许多情况下取决于“驱动”癌基因的激活，如 KRAS、表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）。针对 EGFR 和 ALK 酪氨酸激酶的抑制剂分别对含有 EGFR 基因突变和 ALK 基因融合的 LADC 具有治疗作用。最近，我们和其他人确定 RET 融合基因是 LADC 中的一个新的可靶向驱动基因。RET 融合发生在 1-2%的 LADC 中。现有的美国食品和药物管理局批准的 RET 酪氨酸激酶抑制剂，如 vandetanib（ZD6474）和 cabozantinib（XL184），在体外和体内以及少数患者中均显示出有前景的治疗效果。正在进行临床试验，以研究 RET 酪氨酸激酶抑制剂，如 vandetanib（ZD6474）和 cabozantinib（XL184），在 RET 融合阳性非小细胞肺癌患者中的治疗效果。
