肺大细胞神经内分泌癌的分子分型及临床治疗进展

肺大细胞神经内分泌癌(large cell neuroendocrine carcinoma,LCNEC)发病率较低,占肺恶性肿瘤的2.1%～3.5%,诊断困难,治疗方案的选择尚存争议。LCNEC具有独特的基因谱及转录谱,根据TP53、RB1等基因突变及表达情况可进一步将LCNEC分为RB1野生型和RB1突变型,其中RB1野生型应用非小细胞肺癌(non-small cell lung cancer,NSCLC)常用化疗方案较小细胞肺癌(small cell lung cancer,SCLC)常用方案可显著提高总生存期(overall survival,OS),而RB1突变型应用不同的化疗方案生存均无显著性差异。针对LCNEC的靶向和免疫治疗仅见于小样本的回顾性分析及个案报道。本文对LCNEC相关的分子分型及临床治疗进展予以综述。

Research progress on molecular biology for subtyping and clinical treatment of pulmonary large cell neuroendocrine carcinomas

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of pulmonary malignant tumors, accounting for only 2.1%-3.5% of all pulmonary malignant tumors. The diagnosis of LCNEC is challenging, especially on small biopsy or cytological samples. Due to limited clinical data, the optimal treatment for LCNEC remains unclear. Recent studies have indicated that LCNEC shave a unique molecular profile and can be further divided into two subtypes:RB1-mutant and RB1-wild type. Patients with RB1-wild type LCNECs showed significant longer overall survival (OS) on treatment with non-small cell lung cancer-related regimens than with small cell lung cancer-related regimens. However, different regimens showed similar effects on RB1-mutant LCNECs. Previously, only retrospective studies and case reports have focused on targeted therapy or immunotherapy against LCNEC. Herein, This article will review the progress of molecular typing and clinical treatment of LCNEC.