Clini Cancer Res：抵御卵巢癌的新型药物lurbinectedin（PM01183）

    近日，刊登在国际杂志Clinical Cancer Research上的一项多学科研究中，来自Bellvitge生物研究所和加泰罗尼亚肿瘤研究所的研究人员开发出了一种新型药物，其可以在特定动物模型中检测药物对顺铂耐药的卵巢癌的效果。

    将人类的肿瘤组织植入到裸鼠中相应器官产生的部位，称为正位植入；这种方式可以产生组织学和遗传上的人类肿瘤以及肿瘤的特定扩散模式，但是目前这种植入方式并未实现特定人类肿瘤的效果，而这些特定的肿瘤模型对于开发个体化癌症疗法至关重要。

    在本项研究中，研究者开发的新型模型和技术可以帮助其检测药物lurbinectedin（PM01183）抵御卵巢癌的疗效，lurbinectedin是一种从海洋中提炼出的药物，其可以有效抵御对顺铂耐药的卵巢癌。研究者表示，实验室中正位植入的小鼠模型不仅仅可以加深对癌症的研究，而且可以帮助医药公司开发出新型的抗癌药物。Lurbinectedin目前正在进行II期临床试验。

    研究者最后表示，在小鼠模型中能够产生免疫组化以及遗传学的人流中流对于开发出新型的抗卵巢癌药物是最基本也是最重要的。

与卵巢癌相关的拓展阅读：

• Clini Cancer Res：抵御卵巢癌的新型药物lurbinectedin（PM01183）
• PLoS ONE：细胞刚度能够预测卵巢癌细胞的转移潜力
• Cancer：二甲双胍或可用于卵巢癌治疗
• 大样本卵巢癌肿瘤标志物研究启动
• AIM：建议不需对健康女性进行卵巢癌筛查
更多信息请点击：有关卵巢癌更多资讯

编译自：Animal Models Can Revolutionize the Study of Cancer

doi:10.1158/1078-0432.CCR-12-1513
PMC:
PMID:

Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer

August Vidal3, Clara Muñoz1, María-José Guillén6, Jemina Moretó2, Sara Puertas1, María Martínez-Iniesta1, Agnés Figueras1, Laura Padullés1, Francisco J. García-Rodriguez1, Mireia Berdiel-Acer1, Miguel A. Pujana1, Ramón Salazar4, Marta Gil-Martin4, Lola Martí5, Jordi Ponce5, David G. Molleví1, Gabriel Capella1, Enric Condom3, Francesc Viñals1, Dori Huertas2, Carmen Cuevas6, Manel Esteller2, Pablo Avilés6, and Alberto Villanueva1

Purpose: Epithelial ovarian cancer (EOC) is the fifth leading cause of death in women diagnosed with gynecologic malignancies. The low survival rate is because of its advanced-stage diagnosis and either intrinsic or acquired resistance to standard platinum-based chemotherapy. So, the development of effective innovative therapeutic strategies to overcome cisplatin resistance remains a high priority. Experimental Design: To investigate new treatments in in vivo models reproducing EOCs tumor growth, we generated a preclinical model of ovarian cancer after orthotopic implantation of a primary serous tumor in nude mice. Further, matched model of acquired cisplatin-resistant tumor version was successfully derived in mice. Effectiveness of lurbinectedin (PM01183) treatment, a novel marine-derived DNA minor groove covalent binder, was assessed in both preclinical models as a single and a combined-cisplatin agent. Results: Orthotopically perpetuated tumor grafts mimic the histopathological characteristics of primary patients' tumors and they also recapitulate in mice characteristic features of tumor response to cisplatin treatments. We showed that single lurbinectedin or cisplatin-combined therapies were effective in treating cisplatin-sensitive and cisplatin-resistant preclinical ovarian tumor models. Furthermore, the strongest in vivo synergistic effect was observed for combined treatments, especially in cisplatin-resistant tumors. Lurbinectedin tumor growth inhibition was associated with reduced proliferation, increased rate of aberrant mitosis, and subsequent induced apoptosis. Conclusions: Taken together, preclinical orthotopic ovarian tumor grafts are useful tools for drug development, providing hard evidence that lurbinectedin might be a useful therapy in the treatment of EOC by overcoming cisplatin resistance. Clin Cancer Res; 18(19); 5399–411. ©2012 AACR.

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