Using Cancer Proteomics Data to Identify Gene Candidates for Therapeutic Targeting

Authors

Diana Monsivais
Sydney E Parks
Darshan S Chandrashekar
Sooryanarayana Varambally
Chad J Creighton

Publication Date

5-4-2023

Journal

Oncotarget

DOI

10.18632/oncotarget.28420

PMID

37141409

PMCID

PMC11623401

PubMedCentral® Posted Date

5-4-2023

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Humans, Proteomics, Neoplasms, Genomics, Protein Kinases, proteomics, proteogenomics, multi-omics, cancer, TTK protein kinase

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.