Work

Protocol for modeling acquired resistance to targeted therapeutics in adherent and suspension cancer cell lines via in situ resistance assay

Year: 2024

Type: article

Abstract: 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. 1 and Theard et al. 2 • Acquired resistance to oncogene targeted therapies can be modeled in situ by ISRA • In situ resistance assays are high throughput, cost effective, and scalable • Resistant populations can be isolated from in situ resistance assays (ISRAs) • ISRA can be adopted to test combinations designed to limit acquired resistance Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. 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.

Source: STAR Protocols

DOI: 10.1016/j.xpro.2024.103361