通过原位抗性测定在贴壁和悬浮癌细胞系中模拟获得性靶向治疗抗性的方案。

Sealover Nancy E, Hughes Jacob M, Theard Patricia L, Chatterjee Deepan, Linke Amanda J, Finniff Bridget A, Daley Brianna R, Lewis Robert E, Kortum Robert L

Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Eppley Institute, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.

STAR Protoc. 2024 Dec 20;5(4):103361. doi: 10.1016/j.xpro.2024.103361. Epub 2024 Oct 5.

Acquired resistance to oncogene-targeted therapies is the major driver of mortality for patients with cancer. Here, we present a 6-to-16-week assay to model the development of acquired resistance in adherent and suspension cancer cell lines. We describe steps for determining therapeutic dose, assaying acquired resistance, and testing combination therapies. This protocol is a high-throughput, cost-effective, and scalable method to model acquired drug resistance to established and newly developed therapies. For complete details on the use and execution of this protocol, please refer to Sealover et al. and Theard et al..

对癌基因靶向疗法产生获得性耐药是癌症患者死亡的主要驱动因素。在此，我们展示了一种为期6至16周的检测方法，用于模拟贴壁和悬浮癌细胞系中获得性耐药的发展过程。我们描述了确定治疗剂量、检测获得性耐药以及测试联合疗法的步骤。该方案是一种用于模拟对既定疗法和新开发疗法的获得性耐药的高通量、经济高效且可扩展的方法。有关该方案使用和执行的完整详细信息，请参考西洛弗等人以及西尔德等人的研究。