Using cancer proteomics data to identify gene candidates for therapeutic targeting.

TitleUsing cancer proteomics data to identify gene candidates for therapeutic targeting.
Publication TypeJournal Article
Year of Publication2023
AuthorsMonsivais, D, Parks, SE, Chandrashekar, DS, Varambally, S, Creighton, CJ
JournalOncotarget
Volume14
Pagination399-412
Date Published2023 May 04
ISSN1949-2553
KeywordsGenomics, Humans, Neoplasms, Protein Kinases, Proteomics
Abstract

Gene-level associations obtained from mass-spectrometry-based cancer proteomics datasets represent a resource for identifying gene candidates for functional studies. When recently surveying proteomic correlates of tumor grade across multiple cancer types, we identified specific protein kinases having a functional impact on uterine endometrial cancer cells. This previously published study provides just one template for utilizing public molecular datasets to discover potential novel therapeutic targets and approaches for cancer patients. Proteomic profiling data combined with corresponding multi-omics data on human tumors and cell lines can be analyzed in various ways to prioritize genes of interest for interrogating biology. Across hundreds of cancer cell lines, CRISPR loss of function and drug sensitivity scoring can be readily integrated with protein data to predict any gene's functional impact before bench experiments are carried out. Public data portals make cancer proteomics data more accessible to the research community. Drug discovery platforms can screen hundreds of millions of small molecule inhibitors for those that target a gene or pathway of interest. Here, we discuss some of the available public genomic and proteomic resources while considering approaches to how these could be leveraged for molecular biology insights or drug discovery. We also demonstrate the inhibitory effect of BAY1217389, a TTK inhibitor recently tested in a Phase I clinical trial for the treatment of solid tumors, on uterine cancer cell line viability.

DOI10.18632/oncotarget.28420
Alternate JournalOncotarget
PubMed ID37141409
Grant ListP30 CA125123 / CA / NCI NIH HHS / United States
P20 CA221729 / CA / NCI NIH HHS / United States
R00 HD096057 / HD / NICHD NIH HHS / United States

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