{"doi":"10.1016/j.ctrv.2024.102721","title":"If it’s a target, it’s a pan-cancer target: Tissue is not the issue","abstract":"Cancer is traditionally diagnosed and treated on the basis of its organ of origin (e.g., lung or colon cancer). However, organ-of-origin diagnostics does not reveal the underlying oncogenic drivers. Fortunately, molecular diagnostics have advanced at a breathtaking pace, and it is increasingly apparent that cancer is a disease of the genome. Hence, we now have multiple genomic biomarker-based, tissue-agnostic Food and Drug Administration approvals for both gene- and immune-targeted therapies (larotrectinib/entrectinib, for NTRK fusions; selpercatinib, RET fusions; dabrafenib plus trametinib, BRAFV600E mutations; pembrolizumab/dostarlimab, microsatellite instability; and pembrolizumab for high tumor mutational burden; pemigatinib is also approved for FGFR1-rearranged myeloid/lymphoid neoplasms). There are emerging targets as well, including but not limited to ALK, BRCA and/or homologous repair deficiency, ERBB2 (HER2), IDH1/2, KIT, KRASG12C, NRG1, and VHL. Many tissue-agnostic approvals center on rare/ultra-rare biomarkers (often < 1 % of cancers), necessitating screening hundreds of tumors to find a single one harboring the cognate molecular alteration. Approval has generally been based on small single-arm studies (<30–100 patients) with high response rates (>30 % to > 75 %) of remarkable durability. Because of biomarker rarity, single-gene testing is not practical; next generation sequencing of hundreds of genes must be performed to obtain timely answers. Resistance to biomarker-driven therapeutics is often due to secondary mutations or co-driver gene defects; studies are now addressing the need for customized drug combinations matched to the complex molecular alteration portfolio in each tumor. Future investigation should expand tissue-agnostic therapeutics to encompass both hematologic and solid malignancies and include biomarkers beyond those that are DNA-based.","journal":"Cancer Treatment Reviews","year":2024,"id":421544,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9458,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":235228,"name":"Shumei Kato","orcid":"0000-0003-1193-1815","position":1,"is_corresponding":false},{"id":235244,"name":"Jason K. Sicklick","orcid":"0000-0003-4403-0271","position":2,"is_corresponding":false},{"id":7922,"name":"Scott M. Lippman","orcid":"0000-0002-1643-4124","position":3,"is_corresponding":false},{"id":108759,"name":"Razelle Kurzrock","orcid":"0000-0003-4110-1214","position":4,"is_corresponding":false},{"id":235241,"name":"Jacob J. Adashek","orcid":"0000-0003-4272-312X","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T01:57:41.370244Z","pmid":"38522181","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":[]}