Abstract 3479: The cellular thermal shift assay as a tool for setting indivual treatment schemes

Abstract

Abstract Many cancers respond insufficiently to existing therapies and acquired drug resistance often develops. To address this challenge, a range of different therapeutic strategies is currently in development. Many of these are based on the concept of targeted therapies, where target proteins are drivers of cancer processes or synthetic vulnerabilities of cancer cells. In this project we have used the newly developed CETSA method to monitor levels of drug binding to specific target proteins in tumors and primary cells from breast cancer patients. CETSA is a generic method for evaluating drug binding to target proteins in cells and tissues. The technique is based on the physical phenomenon of ligand-induced thermal stabilization of target proteins. Using this technique, it is possible to look at interactions between a drug and protein of interest without having to label them. Previously, we have validated drug binding in mammalian cancer cell lines for a set of important clinical targets and shown that a range of critical factors that are important for drug development can be identified at the target engagement level, including drug transport and activation, off-target effects, drug resistance as well as drug distribution in animal tissues. By using different drugs and amounts we now have preliminary data suggesting that CETSA could be used as a tool for optimizing treatment schemes for individual care and for detecting resistance development at an early stage. Citation Format: Daniel M. Molina, Pär Nordlund. The cellular thermal shift assay as a tool for setting indivual treatment schemes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3479. doi:10.1158/1538-7445.AM2014-3479