MassIVE MSV000093533

Partial Public PXD046959

Illuminating phenotypic drug responses of sarcoma cells to kinase inhibitors by phosphoproteomics-2

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Description

Kinase inhibitors (KIs) are important cancer drugs but often display polypharmacology that is molecularly not understood. This disconnect is particularly apparent in cancer entities such as sarcomas for which the oncogenic drivers are often not clear. To investigate more systematically how the cellular proteotypes of sarcoma cells shape their response to molecularly targeted drugs, we profiled the proteomes and phosphoproteomes of 17 sarcoma cell lines and screened the same cells against 150 cancer drugs. The resulting 2,550 phenotypic drug profiles revealed distinct drug responses and the cellular activity landscapes derived from deep (phospho)proteomes (9-10,000 proteins and 10-27,000 phosphorylation sites per cell line) enabled several lines of analysis. For instance, connecting the (phospho)proteomic data with drug responses revealed known and novel mechanisms of action (MoAs) of kinase inhibitors and identified markers of drug sensitivity or resistance. All data is publically accessible via an interactive web application that enables exploration of this rich molecular resource for better understanding active signalling pathways in sarcoma cells, identifying treatment response predictors, and revealing novel MoA of clinical KIs. [doi:10.25345/C5M902D5T] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: phosphoproteomics ; kinase inhibitor ; sarcoma ; drug response ; proteotype

Contact

Principal Investigators:
(in alphabetical order) 		Bernhard Kuster, Chair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Germany
Submitting User: cylee

Publications

Lee CY, The M, Meng C, Bayer FP, Putzker K, Müller J, Streubel J, Woortman J, Sakhteman A, Resch M, Schneider A, Wilhelm S, Kuster B.
Illuminating phenotypic drug responses of sarcoma cells to kinase inhibitors by phosphoproteomics.
Mol Syst Biol. 2024 Jan;20(1):28-55. Epub 2023 Dec 18.

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