Xu Dongbo, Li Qiang
Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA.
Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA.
Cancer Heterog Plast. 2025;2(1). doi: 10.47248/chp2502010005. Epub 2025 Mar 6.
Neuroendocrine bladder cancer (NEBC) is a rare but highly aggressive cancer, representing approximately 1% of urinary bladder cancer. The most common NEBC is small cell bladder cancer (SCBC), characterized by high rates of recurrence, chemotherapy resistance, and early mortality. SCBC is histologically identical to small cell lung cancer (SCLC) but remains significantly understudied. Advances in next-generation sequencing techniques have partially elucidated the molecular characteristics of NEBC and identified druggable targets. This review compiles recent studies on human NEBC samples, summarizing key findings on their genomic alterations and molecular subtyping. Notably, it highlights specific mutations in the promoter and epigenetic modifiers in NEBC, as well as molecular subtyping based on lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. Furthermore, this review explores the significant tumor heterogeneity and cellular plasticity observed in NEBC and discusses its cell of origin and potential therapeutic targets (MET inhibitor or DLL3) identified by preclinical NEBC models. Emerging evidence suggests that NEBC may share a common origin with urothelial carcinoma (UC), arising from a UC precursor. Advancing our understanding of NEBC tumorigenesis and identifying druggable targets will enhance treatment outcomes for patients with NEBC.
神经内分泌膀胱癌（NEBC）是一种罕见但侵袭性很强的癌症，约占膀胱癌的1%。最常见的NEBC是小细胞膀胱癌（SCBC），其特点是复发率高、化疗耐药且早期死亡率高。SCBC在组织学上与小细胞肺癌（SCLC）相同，但仍未得到充分研究。新一代测序技术的进展部分阐明了NEBC的分子特征并确定了可成药靶点。本综述汇编了关于人类NEBC样本的最新研究，总结了其基因组改变和分子亚型的关键发现。值得注意的是，它强调了NEBC中启动子和表观遗传修饰因子的特定突变，以及基于谱系特异性转录因子（包括ASCL1、NEUROD1和POU2F3）的分子亚型。此外，本综述探讨了在NEBC中观察到的显著肿瘤异质性和细胞可塑性，并讨论了其起源细胞以及临床前NEBC模型确定的潜在治疗靶点（MET抑制剂或DLL3）。新出现的证据表明，NEBC可能与尿路上皮癌（UC）有共同起源，源自UC前体。加深我们对NEBC肿瘤发生的理解并确定可成药靶点将提高NEBC患者的治疗效果。
