Gerber David E, Paik Paul K, Dowlati Afshin
From The University of Texas Southwestern Medical Center, Dallas, TX; Memorial Sloan Kettering Cancer Center, New York, NY; Case Western Reserve University, Cleveland, OH.
Am Soc Clin Oncol Educ Book. 2015:147-62. doi: 10.14694/EdBook_AM.2015.35.147.
Lung cancer encompasses a diverse spectrum of histologic subtypes. Until recently, the majority of therapeutic advances were limited to the minority of patients with adenocarcinoma. With the advent of comprehensive genomic profiling of squamous and small cell lung cancers, new therapeutic targets have emerged. For squamous tumors, the most promising of these include fibroblast growth factor receptor (FGFR), the phosphatidylinositol 3-kinase (PI3K) pathway, discoidin domain receptor 2 (DDR2), and G1/S checkpoint regulators. In 2014, the antiangiogenic agent ramucirumab was approved for all non-small cell lung cancer (NSCLC) histologies, including squamous tumors. Immunotherapeutic approaches also appear to be promising for these cases. Genomic analysis of small cell lung cancer has revealed a high mutation burden, but relatively few druggable driver oncogenic alterations. Current treatment strategies under investigation are focusing on targeting mitotic, cell cycle, and DNA repair regulation, as well as immunotherapy. Pulmonary neuroendocrine tumors represent a diverse spectrum of diseases that may be treated with somatostatin analogs, cytotoxic agents, and molecularly targeted therapies. Radiolabeled somatostatin analogs and combinations with mammalian target of rapamycin (mTOR) inhibitors also show potential. Large cell neuroendocrine tumors share numerous clinical, pathologic, and molecular features with small cell lung cancer; however, whether they should be treated similarly or according to a NSCLC paradigm remains a matter of debate.
肺癌包含多种组织学亚型。直到最近，大多数治疗进展都局限于少数腺癌患者。随着鳞状细胞癌和小细胞肺癌全面基因组分析的出现，新的治疗靶点已经出现。对于鳞状肿瘤，其中最有前景的靶点包括成纤维细胞生长因子受体（FGFR）、磷脂酰肌醇3激酶（PI3K）通路、盘状结构域受体2（DDR2）和G1/S期检查点调节因子。2014年，抗血管生成药物雷莫西尤单抗被批准用于所有非小细胞肺癌（NSCLC）组织学类型，包括鳞状肿瘤。免疫治疗方法在这些病例中似乎也很有前景。小细胞肺癌的基因组分析显示其突变负荷高，但可靶向治疗的驱动致癌改变相对较少。目前正在研究的治疗策略集中在靶向有丝分裂、细胞周期和DNA修复调节，以及免疫治疗。肺神经内分泌肿瘤代表了多种疾病，可用生长抑素类似物、细胞毒性药物和分子靶向疗法进行治疗。放射性标记的生长抑素类似物以及与雷帕霉素靶蛋白（mTOR）抑制剂的联合应用也显示出潜力。大细胞神经内分泌肿瘤与小细胞肺癌有许多临床、病理和分子特征；然而，它们是应采用相似的治疗方法还是按照非小细胞肺癌的模式进行治疗仍存在争议。
