Calles Antonio, Calvo Emiliano, Santamaría Nuñez Gema, Costanzo Federico, Guillén María José, Martinez Diez Marta, Gupta Aparna, Cuevas Carmen, Egly Jean-Marc, Avilés Pablo
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain.
Mol Cancer Ther. 2025 Jun 4;24(6):828-839. doi: 10.1158/1535-7163.MCT-24-0050.
Lurbinectedin is a selective inhibitor of oncogenic transcription approved for the treatment of adult patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. Preclinical data provide evidence for lurbinectedin exerting its actions in a unique manner that involves oncogenic transcription inhibition, DNA damage, reshaping of the tumor microenvironment, and inducing anticancer immunity. Understanding the mechanism of action has facilitated the rational combination of lurbinectedin and anticancer therapies with complementary modes of action, in order to obtain synergistic effects that could potentially lead to improved efficacy. This review evaluates the mechanism of action for lurbinectedin and provides an overview of the therapeutic landscape with regards to lurbinectedin combination therapies for the treatment of small cell lung cancer based on data from preclinical and clinical studies.
鲁比卡丁是一种获批用于治疗铂类化疗期间或之后病情进展的成年转移性小细胞肺癌患者的致癌转录选择性抑制剂。临床前数据表明,鲁比卡丁以独特的方式发挥作用,包括抑制致癌转录、造成DNA损伤、重塑肿瘤微环境以及诱导抗癌免疫。对其作用机制的了解有助于将鲁比卡丁与具有互补作用模式的抗癌疗法进行合理联合,以获得可能提高疗效的协同效应。本综述评估了鲁比卡丁的作用机制,并根据临床前和临床研究数据,概述了鲁比卡丁联合疗法治疗小细胞肺癌的治疗前景。