小柯机器人

英国威康桑格研究所Mathew J. Garnett研究小组提出了乳腺癌、结肠癌和胰腺癌细胞的有效药物联用。相关论文于2022年2月23日在线发表在《自然》杂志上。

研究人员评估了2025种临床相关双药组合的效力和疗效，产生了一个包括125种分子特征的乳腺癌、结直肠癌和胰腺癌细胞系的数据集。结果表明，药物之间的协同作用是罕见的，并且高度依赖于环境，而靶向药物的组合最有可能产生协同作用。研究人员结合多组学分子特征来确定了组合生物标志物，并指定协同作用的药物组合及其活性背景，包括在基底样乳腺癌和微卫星稳定或KRAS突变的结肠癌。结果显示，伊立替康和CHEK1抑制在微卫星稳定或KRAS-TP53双突变的结肠癌细胞中具有协同作用，导致细胞凋亡和抑制肿瘤异种移植生长。这项研究在不同的分子亚群中确定了具有临床意义的有效药物组合，是指导开发组合药物治疗的一种资源。

据介绍，抗癌药物的组合可以克服抗药性并提供新的治疗方法。潜在药物组合的数量大大超过了可以进行临床试验的数量。系统地确定有效的组合以及它们最有效的组织和分子背景可以加速组合治疗的发展。

附：英文原文

Title: Effective drug combinations in breast, colon and pancreatic cancer cells

Author: Jaaks, Patricia, Coker, Elizabeth A., Vis, Daniel J., Edwards, Olivia, Carpenter, Emma F., Leto, Simonetta M., Dwane, Lisa, Sassi, Francesco, Lightfoot, Howard, Barthorpe, Syd, van der Meer, Dieudonne, Yang, Wanjuan, Beck, Alexandra, Mironenko, Tatiana, Hall, Caitlin, Hall, James, Mali, Iman, Richardson, Laura, Tolley, Charlotte, Morris, James, Thomas, Frances, Lleshi, Ermira, Aben, Nanne, Benes, Cyril H., Bertotti, Andrea, Trusolino, Livio, Wessels, Lodewyk, Garnett, Mathew J.

Issue&Volume: 2022-02-23

Abstract: Combinations of anti-cancer drugs can overcome resistance and provide new treatments1,2. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable or KRAS-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or KRAS–TP53 double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.

DOI: 10.1038/s41586-022-04437-2

Source: https://www.nature.com/articles/s41586-022-04437-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html