Unveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer.

IF 5.3 2区医学 Q1 ONCOLOGY Molecular Cancer Therapeutics Pub Date : 2024-12-05 DOI:10.1158/1535-7163.MCT-24-0050

Antonio Calles, Emiliano Calvo, Gema Santamaría Nuñez, Federico Costanzo, María José Guillén, Marta Martinez Diez, Aparna Gupta, Carmen Cuevas, Jean-Marc Egly, Pablo Aviles

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Abstract

Lurbinectedin is a selective inhibitor of oncogenic transcription approved for the treatment of adult patients with metastatic small cell lung cancer (SCLC) 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 (MoA) 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 MoA for lurbinectedin and provides an overview of the therapeutic landscape with regards to lurbinectedin combination therapies for the treatment of SCLC based on data from preclinical and clinical studies.

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揭示Lurbinectedin在小细胞肺癌中的作用机制及其联合治疗的潜力。

Lurbinectedin是一种选择性的致癌转录抑制剂，被批准用于治疗在铂基化疗期间或之后疾病进展的转移性小细胞肺癌（SCLC）的成人患者。临床前数据证明，lurbinectedin以一种独特的方式发挥其作用，包括致癌转录抑制、DNA损伤、肿瘤微环境重塑和诱导抗癌免疫。了解作用机制（MoA）有助于合理地将lurbinectedin与具有互补作用模式的抗癌药物联合使用，以获得可能导致疗效提高的协同效应。本综述基于临床前和临床研究的数据，评估了lurbinectedin的MoA，并概述了lurbinectedin联合疗法治疗SCLC的治疗前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer Therapeutics 医学-肿瘤学

CiteScore

11.20

自引率

1.80%

发文量

331

审稿时长

3 months

期刊介绍： Molecular Cancer Therapeutics will focus on basic research that has implications for cancer therapeutics in the following areas: Experimental Cancer Therapeutics, Identification of Molecular Targets, Targets for Chemoprevention, New Models, Cancer Chemistry and Drug Discovery, Molecular and Cellular Pharmacology, Molecular Classification of Tumors, and Bioinformatics and Computational Molecular Biology. The journal provides a publication forum for these emerging disciplines that is focused specifically on cancer research. Papers are stringently reviewed and only those that report results of novel, timely, and significant research and meet high standards of scientific merit will be accepted for publication.