{"doi":"10.1016/j.neo.2023.100910","title":"Genomics driven precision oncology in advanced biliary tract cancer improves survival","abstract":"BACKGROUND: Biliary tract cancers (BTCs) including intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder cancer, are rare but aggressive malignancies with few effective standard of care therapies. METHODS: We implemented integrative clinical sequencing of advanced BTC tumors from 124 consecutive patients who progressed on standard therapies (N=92 with MI-ONCOSEQ and N=32 with commercial gene panels) enrolled between 2011-2020. RESULTS: Genomic profiling of paired tumor and normal DNA and tumor transcriptome (RNA) sequencing identified actionable somatic and germline genomic alterations in 54 patients (43.5%), and potentially actionable alterations in 79 (63.7%) of the cohort. Of these, patients who received matched targeted therapy (22; 40.7%) had a median overall survival of 28.1 months compared to 13.3 months in those who did not receive matched targeted therapy (32; P < 0.01), or 13.9 months in those without actionable mutations (70; P < 0.01). Additionally, we discovered recurrent activating mutations in FGFR2, and a novel association between KRAS and BRAF mutant tumors with high expression of immune modulatory protein NT5E (CD73) that may represent novel therapeutic avenues. CONCLUSIONS: Overall, the identification of actionable/ potentially actionable aberrations in a large proportion of cases, and improvement in survival with precision oncology supports molecular analysis and clinical sequencing for all patients with advanced BTC.","journal":"Neoplasia","year":2023,"id":341149,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":108221,"name":"Pankaj Vats","orcid":"0000-0001-8441-7732","position":1,"is_corresponding":false},{"id":714507,"name":"Nguyen H. Tran","orcid":"0000-0002-6104-6489","position":2,"is_corresponding":false},{"id":415616,"name":"Dan R. Robinson","orcid":"0000-0002-2337-7439","position":3,"is_corresponding":false},{"id":225399,"name":"Valerie Gunchick","orcid":"0000-0002-9392-0644","position":4,"is_corresponding":false},{"id":415615,"name":"Yi‐Mi Wu","orcid":"0000-0002-3789-4445","position":5,"is_corresponding":false},{"id":262041,"name":"Xuhong Cao","orcid":"0000-0002-2455-3086","position":6,"is_corresponding":false},{"id":292343,"name":"Ning Yu","orcid":"0000-0002-3046-4338","position":7,"is_corresponding":false},{"id":618684,"name":"Rui Wang","orcid":"0000-0002-5356-9685","position":8,"is_corresponding":false},{"id":1077205,"name":"Erica Rabban","orcid":null,"position":9,"is_corresponding":false},{"id":1076668,"name":"Janice F. Bell","orcid":"0000-0002-6528-0686","position":10,"is_corresponding":false},{"id":356643,"name":"Sunita Shankar","orcid":"0000-0001-8743-7480","position":11,"is_corresponding":false},{"id":108220,"name":"Rahul Mannan","orcid":"0000-0002-6642-0468","position":12,"is_corresponding":false},{"id":355721,"name":"Yuping Zhang","orcid":"0000-0002-8600-9879","position":13,"is_corresponding":false},{"id":840227,"name":"Mark M. Zalupski","orcid":"0000-0002-2114-9352","position":14,"is_corresponding":false},{"id":51796,"name":"Arul M. Chinnaiyan","orcid":"0000-0001-9282-3415","position":15,"is_corresponding":false},{"id":225417,"name":"Vaibhav Sahai","orcid":"0000-0003-1892-1548","position":16,"is_corresponding":false},{"id":51858,"name":"Chandan Kumar‐Sinha","orcid":"0000-0002-8696-3400","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:11:03.393978Z","pmid":"37267699","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":[]}