PDF(Pubmed)
Abstract：
Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following the development of lurbinectedin resistance showed a new actionable ERBB2 alteration without significant change in the tumor mutation burden (six mutations/Mb). The present report suggests that lurbinectedin may be active and should be further explored in SCBC harboring TP53 mutations and amplifications in E2F3 and MYC family complexes.
摘要：
小细胞膀胱癌（SCBC）是一种罕见且侵袭性的疾病，经常用铂/依托泊苷为基础的化疗。关键的分子驱动因素包括抑癌基因（TP53，RB1）的失活和原癌基因（MYC）的扩增。我们报告了一名SCBC患者，他对lurbinectedin达到了客观和长期的反应，已被批准用于转移性小细胞肺癌，顺铂/依托泊苷和纳武单抗/伊匹单抗发生疾病进展后。在lurbinectedin启动之前对转移性活检的基因组分析显示TP53突变和细胞周期调节因子E2F3和MYCL的扩增。lurbinectedin耐药性发展后的重复活检显示了新的可操作的ERBB2改变，而肿瘤突变负荷没有显着变化（六个突变/Mb）。本报告表明，lurbinectedin可能具有活性，应在具有TP53突变和E2F3和MYC家族复合物扩增的SCBC中进一步研究。
