Saito Motonobu, Suzuki Hiroyuki, Kono Koji, Takenoshita Seiichi, Kohno Takashi
Division of Genome Biology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 1040045, Japan.
Department of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
Surg Today. 2018 Jan;48(1):1-8. doi: 10.1007/s00595-017-1497-7. Epub 2017 Mar 9.
Lung adenocarcinoma (LADC) is a cancer treatable using targeted therapies against driver gene aberrations. EGFR mutations and ALK fusions are frequent gene aberrations in LADC, and personalized therapies against those aberrations have become a standard therapy. These targeted therapies have shown significant positive efficacy and tolerable toxicity compared to conventional chemotherapy, so it is necessary to identify additional druggable genetic aberrations. Other than EGFR mutations and ALK fusions, mutations in KRAS, HER2, and BRAF, and driver fusions involving RET and ROS1, have also been identified in LADC. Interestingly, the frequency of driver gene aberrations differs according to ethnicity, sex, and smoking, which leads to differences in treatment efficacy. To date, several molecular-targeted drugs against driver genes have been developed, and several clinical trials have been conducted to evaluate the efficacy. However, targeted therapies against driver-gene-negative cases have not yet been well developed. Efforts to identify a new druggable target for such cases are currently underway. Furthermore, immune checkpoint blockade therapy might be effective for driver-negative cases, especially those with accumulated mutations.
肺腺癌（LADC）是一种可通过针对驱动基因畸变的靶向疗法进行治疗的癌症。EGFR突变和ALK融合是LADC中常见的基因畸变，针对这些畸变的个性化疗法已成为标准疗法。与传统化疗相比，这些靶向疗法已显示出显著的积极疗效和可耐受的毒性，因此有必要识别其他可药物化的基因畸变。除了EGFR突变和ALK融合外，LADC中还发现了KRAS、HER2和BRAF的突变，以及涉及RET和ROS1的驱动融合。有趣的是，驱动基因畸变的频率因种族、性别和吸烟情况而异，这导致了治疗效果的差异。迄今为止，已经开发了几种针对驱动基因的分子靶向药物，并进行了多项临床试验来评估其疗效。然而，针对驱动基因阴性病例的靶向疗法尚未得到充分发展。目前正在努力为这类病例寻找新的可药物化靶点。此外，免疫检查点阻断疗法可能对驱动基因阴性病例有效，尤其是那些有累积突变的病例。
