Language
English
Publication Date
8-8-2024
Journal
Cell
DOI
10.1016/j.cell.2024.05.039
PMID
38917788
PMCID
PMC12010439
PubMedCentral® Posted Date
8-8-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Fewer than 200 proteins are targeted by cancer drugs approved by the Food and Drug Administration (FDA). We integrate Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomics data from 1,043 patients across 10 cancer types with additional public datasets to identify potential therapeutic targets. Pan-cancer analysis of 2,863 druggable proteins reveals a wide abundance range and identifies biological factors that affect mRNA-protein correlation. Integration of proteomic data from tumors and genetic screen data from cell lines identifies protein overexpression- or hyperactivation-driven druggable dependencies, enabling accurate predictions of effective drug targets. Proteogenomic identification of synthetic lethality provides a strategy to target tumor suppressor gene loss. Combining proteogenomic analysis and MHC binding prediction prioritizes mutant KRAS peptides as promising public neoantigens. Computational identification of shared tumor-associated antigens followed by experimental confirmation nominates peptides as immunotherapy targets. These analyses, summarized at https://targets.linkedomics.org, form a comprehensive landscape of protein and peptide targets for companion diagnostics, drug repurposing, and therapy development.
Keywords
Humans, Proteogenomics, Neoplasms, Molecular Targeted Therapy, Immunotherapy, Antigens, Neoplasm, Cell Line, Tumor, Antineoplastic Agents, Peptides, Proteomics, Proto-Oncogene Proteins p21(ras)
Published Open-Access
yes
Recommended Citation
Savage, Sara R; Yi, Xinpei; Lei, Jonathan T; et al., "Pan-Cancer Proteogenomics Expands the Landscape of Therapeutic Targets" (2024). Faculty and Staff Publications. 4617.
https://digitalcommons.library.tmc.edu/baylor_docs/4617