Durable Objective Response to Lurbinectedin in Small Cell Bladder Cancer with TP53 Mutation: A Molecular-Directed Strategy

Autor: Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R. Wilson, Sagar A. Naik, Vivek Subbiah, Matthew T. Campbell, Pavlos Msaouel, Parminder Singh, Omar Alhalabi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Current Oncology, Vol 31, Iss 6, Pp 3342-3349 (2024)
Druh dokumentu: article
ISSN: 1718-7729
1198-0052
DOI: 10.3390/curroncol31060254
Popis: 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.
Databáze: Directory of Open Access Journals
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