{"doi":"10.1016/j.omto.2023.08.008","title":"JNTX-101, a novel albumin-encapsulated gemcitabine prodrug, is efficacious and operates via caveolin-1-mediated endocytosis","abstract":"Albumin is an attractive candidate carrier for the development of novel therapeutic drugs. Gemcitabine has been FDA approved for the treatment of solid tumors; however, new drugs that optimize gemcitabine delivery are not available for clinical use. The aim of this study was to test the efficacy of a novel albumin-encapsulated gemcitabine prodrug, JNTX-101, and investigate whether Cav-1 expression predicts the therapeutic efficacy of JNTX-101. We first determined the treatment efficacy of JNTX-101 in a panel of pancreatic/lung cancer cell lines and found that increases in Cav-1 expression resulted in higher uptake of albumin, while Cav-1 depletion attenuated the sensitivity of cells to JNTX-101. In addition, decreased Cav-1 expression markedly reduced JNTX-101-induced apoptotic cell death in a panel of cells, particularly in low-serum conditions. Furthermore, we tested the therapeutic efficacy of JNTX-101 in xenograft models and the role of Cav-1 in JNTX-101 sensitivity using a Tet-on-inducible tumor model in vivo . Our data suggest that JNTX-101 effectively inhibits cell viability and tumor growth, and that Cav-1 expression dictates optimal sensitivity to JNTX-101. These data indicate that Cav-1 correlates with JNTX-101 sensitivity, especially under nutrient-deprived conditions, and supports a role for Cav-1 as a predictive biomarker for albumin-encapsulated therapeutics such as JNTX-101.","journal":"Molecular Therapy — Oncolytics","year":2023,"id":371519,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"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":753758,"name":"Sergio Corrales-Guerrero","orcid":"0000-0002-5107-3475","position":1,"is_corresponding":false},{"id":1131522,"name":"Verónica Castro-Aceituno","orcid":"0000-0002-5285-3975","position":2,"is_corresponding":false},{"id":1121552,"name":"Sindhu Nair","orcid":"0000-0002-5350-1664","position":3,"is_corresponding":false},{"id":555540,"name":"Daniel C. Maneval","orcid":"0000-0002-8143-9992","position":4,"is_corresponding":false},{"id":1132082,"name":"Curtis A. Monnig","orcid":null,"position":5,"is_corresponding":false},{"id":1132083,"name":"Patrick Kearney","orcid":null,"position":6,"is_corresponding":false},{"id":1131523,"name":"Sam Ellis","orcid":"0000-0003-3946-1464","position":7,"is_corresponding":false},{"id":1132084,"name":"Nicholas Raheja","orcid":null,"position":8,"is_corresponding":false},{"id":1132085,"name":"Neil Raheja","orcid":null,"position":9,"is_corresponding":false},{"id":288341,"name":"Terence M. Williams","orcid":"0000-0002-1020-0845","position":10,"is_corresponding":false},{"id":753759,"name":"Tiantian Cui","orcid":"0000-0003-0651-7193","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T01:15:49.453761Z","pmid":"37674628","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":[]}