Abstract 3933: CETSA as a diagnostic tool to guide personalized breast cancer therapy

Abstract

Abstract The increased knowledge of fundamental cancer biology has translated into the development of a large number of targeted drugs. However, the potential for breakthroughs in cancer therapy is hampered by the lack of knowledge regarding which patients would benefit from a specific drug. Therefore, there is a need of diagnostic tools that can predict if the individual patient will respond or develop resistance to a specific treatment plan. In the present project we aim to meet this challenge by developing stringent clinical diagnostic assays for assessing target engagement (TE; i.e. drug binding to its target protein in situ) of current and emerging drugs in breast cancer treatment. The key to develop these clinical TE assays is our novel technology Cellular Thermal Shift Assay (CETSA). This method allow for the first time direct monitoring of biophysical drug TE in cells, animals and patient samples. The main aim of the project is to correlate the results obtained by CETSA on breast cancer biopsies to the treatment outcome for the biopsied patient, with the goal of creating a diagnostic tool for guiding personalized breast cancer treatment. We also aim to identify new biomarkers of efficacy and resistance for specific drugs, by implementing proteome wide CETSA based on a quantitative mass spectrometry read out. Our recent data demonstrates that CETSA can assess TE in intact cells of drugs commonly used in breast cancer treatment, such as microtubule inhibitors, anthracyclins and CDK4/6 inhibitors. Further we show that CETSA can be applied in vivo on human breast cancer Xenografts and breast cancer patient samples. These data further strengthens the potential of CETSA to become a valuable clinical tool and complement other diagnostic methods to improve efficacy and minimize adverse effects of cancer drugs. Citation Format: Anette Öberg, Henriette Laursen, Sylvia Packham, Daniel Martinez Molina, Takahiro Seki, Yihai Cao, Johan Hartman, Jonas Bergh, Pär Nordlund, Sara Lööf. CETSA as a diagnostic tool to guide personalized breast cancer therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3933.