{"doi":"10.3390/ph16030389","title":"A Bitter Taste Receptor as a Novel Molecular Target on Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma","abstract":"Cancer-associated fibroblasts (CAFs) execute diverse and complex functions in cancer progression. While reprogramming the crosstalk between CAFs and cancer epithelial cells is a promising avenue to evade the adverse effects of stromal depletion, drugs are limited by their suboptimal pharmacokinetics and off-target effects. Thus, there is a need to elucidate CAF-selective cell surface markers that can improve drug delivery and efficacy. Here, functional proteomic pulldown with mass spectrometry was used to identify taste receptor type 2 member 9 (TAS2R9) as a CAF target. TAS2R9 target characterization included binding assays, immunofluorescence, flow cytometry, and database mining. Liposomes conjugated to a TAS2R9-specific peptide were generated, characterized, and compared to naked liposomes in a murine pancreatic xenograft model. Proof-of-concept drug delivery experiments demonstrate that TAS2R9-targeted liposomes bind with high specificity to TAS2R9 recombinant protein and exhibit stromal colocalization in a pancreatic cancer xenograft model. Furthermore, the delivery of a CXCR2 inhibitor by TAS2R9-targeted liposomes significantly reduced cancer cell proliferation and constrained tumor growth through the inhibition of the CXCL-CXCR2 axis. Taken together, TAS2R9 is a novel cell-surface CAF-selective target that can be leveraged to facilitate small-molecule drug delivery to CAFs, paving the way for new stromal therapies.","journal":"Pharmaceuticals","year":2023,"id":355536,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"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":1103478,"name":"Samantha M. Perez","orcid":"0000-0001-5888-2016","position":1,"is_corresponding":false},{"id":327134,"name":"Siva Sai Krishna Dasa","orcid":"0000-0002-9894-6333","position":2,"is_corresponding":false},{"id":65261,"name":"Sarah Hall","orcid":null,"position":3,"is_corresponding":false},{"id":1103913,"name":"Danielle B. Heckert","orcid":null,"position":4,"is_corresponding":false},{"id":1103479,"name":"Brian P. Murphy","orcid":"0000-0003-2728-8553","position":5,"is_corresponding":false},{"id":225419,"name":"Howard C. Crawford","orcid":"0000-0001-9360-3019","position":6,"is_corresponding":false},{"id":318257,"name":"Kimberly A. Kelly","orcid":"0000-0002-1146-3137","position":7,"is_corresponding":false},{"id":317871,"name":"Lindsey T. Brinton","orcid":"0000-0002-4149-9384","position":8,"is_corresponding":false},{"id":769195,"name":"Jessica Hung","orcid":"0000-0002-7815-1082","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:13:16.394812Z","pmid":"36986488","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":[]}