{"doi":"10.1186/s13073-018-0564-z","title":"Integrative omics analyses broaden treatment targets in human cancer","abstract":"<h4>Background</h4>Although large-scale, next-generation sequencing (NGS) studies of cancers hold promise for enabling precision oncology, challenges remain in integrating NGS with clinically validated biomarkers.<h4>Methods</h4>To overcome such challenges, we utilized the Database of Evidence for Precision Oncology (DEPO) to link druggability to genomic, transcriptomic, and proteomic biomarkers. Using a pan-cancer cohort of 6570 tumors, we identified tumors with potentially druggable biomarkers consisting of drug-associated mutations, mRNA expression outliers, and protein/phosphoprotein expression outliers identified by DEPO.<h4>Results</h4>Within the pan-cancer cohort of 6570 tumors, we found that 3% are druggable based on FDA-approved drug-mutation interactions in specific cancer types. However, mRNA/phosphoprotein/protein expression outliers and drug repurposing across cancer types suggest potential druggability in up to 16% of tumors. The percentage of potential drug-associated tumors can increase to 48% if we consider preclinical evidence. Further, our analyses showed co-occurring potentially druggable multi-omics alterations in 32% of tumors, indicating a role for individualized combinational therapy, with evidence supporting mTOR/PI3K/ESR1 co-inhibition and BRAF/AKT co-inhibition in 1.6 and 0.8% of tumors, respectively. We experimentally validated a subset of putative druggable mutations in BRAF identified by a protein structure-based computational tool. Finally, analysis of a large-scale drug screening dataset lent further evidence supporting repurposing of drugs across cancer types and the use of expression outliers for inferring druggability.<h4>Conclusions</h4>Our results suggest that an integrated analysis platform can nominate multi-omics alterations as biomarkers of druggability and aid ongoing efforts to bring precision oncology to patients.","journal":"Genome Medicine","year":2018,"id":4310,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.37,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2018-07-27","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":75979,"name":"Sam Qiancheng Sun","orcid":null,"position":1,"is_corresponding":false},{"id":1998,"name":"Kuan-lin Huang","orcid":"0000-0002-3237-4248","position":2,"is_corresponding":false},{"id":44657,"name":"Clara Oh","orcid":"0000-0001-6213-8935","position":3,"is_corresponding":false},{"id":13229,"name":"Matthew H. 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Wendl","orcid":"0000-0002-5694-2668","position":14,"is_corresponding":false},{"id":2222,"name":"David Fenyö","orcid":"0000-0001-5049-3825","position":16,"is_corresponding":false},{"id":44661,"name":"Reid R. Townsend","orcid":null,"position":17,"is_corresponding":false},{"id":18437,"name":"John F. Dipersio","orcid":"0000-0002-0429-3133","position":18,"is_corresponding":false},{"id":15995,"name":"Feng Chen","orcid":"0000-0002-2699-7190","position":19,"is_corresponding":false},{"id":32248,"name":"Fred R. Hirsch","orcid":"0000-0002-9213-4414","position":20,"is_corresponding":false},{"id":18433,"name":"John S. Welch","orcid":"0000-0001-6656-3672","position":22,"is_corresponding":false},{"id":2228,"name":"X. Cynthia","orcid":"0000-0002-8156-7492","position":23,"is_corresponding":false},{"id":44662,"name":"Samuel H. Payne","orcid":"0000-0002-8351-1994","position":24,"is_corresponding":false},{"id":44655,"name":"Sohini Sengupta","orcid":"0000-0001-7291-829X","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}