{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Roy Chaudhuri T"],"funding":["National Center for Advancing Translational Sciences","Center for Protein Therapeutics, University at Buffalo","NCATS NIH HHS","Cancer Research UK","Health and Social Care Northern Ireland","Science Foundation Ireland","Medical Research Council","Roswell Park Comprehensive Cancer Center","National Cancer Institute","NCI NIH HHS","New York State Stem Cell Science","Division of Chemical, Bioengineering, Environmental, and Transport Systems"],"pagination":["1367-1381"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11019863"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(7)"],"pubmed_abstract":["<h4>Purpose</h4>Paracrine activation of pro-fibrotic hedgehog (HH) signaling in pancreatic ductal adenocarcinoma (PDAC) results in stromal amplification that compromises tumor drug delivery, efficacy, and patient survival. Interdiction of HH-mediated tumor-stroma crosstalk with smoothened (SMO) inhibitors (SHHi) \"primes\" PDAC patient-derived xenograft (PDX) tumors for increased drug delivery by transiently increasing vascular patency/permeability, and thereby macromolecule delivery. However, patient tumor isolates vary in their responsiveness, and responders show co-induction of epithelial-mesenchymal transition (EMT). We aimed to identify the signal derangements responsible for EMT induction and reverse them and devise approaches to stratify SHHi-responsive tumors noninvasively based on c"],"journal":["Clinical cancer research : an official journal of the American Association for Cancer Research"],"pubmed_title":["Dual-Hit Strategy for Therapeutic Targeting of Pancreatic Cancer in Patient-Derived Xenograft Tumors."],"pmcid":["PMC11019863"],"funding_grant_id":["P30CA016056","C026415","R21 CA234775","MC_PC_15013","UL1TR001412","R21CA168454","UL1 TR001412","R01 CA198096","C026714","R21 CA168454","C11884/A24367","R01CA198096","CBET-1706050","P30 CA016056","SFI/14/US/B2997","STL/5010/14","CBET-1555720","R21CA234775"],"pubmed_authors":["Quinn GP","Lin Q","Scott CJ","Spernyak JA","Ma WW","Stachowiak MK","Rosario SR","McDade SS","Greene MK","Stachowiak EK","Straubinger RM","Roy Chaudhuri T","Clynes M"],"additional_accession":[]},"is_claimable":false,"name":"Dual-Hit Strategy for Therapeutic Targeting of Pancreatic Cancer in Patient-Derived Xenograft Tumors.","description":"<h4>Purpose</h4>Paracrine activation of pro-fibrotic hedgehog (HH) signaling in pancreatic ductal adenocarcinoma (PDAC) results in stromal amplification that compromises tumor drug delivery, efficacy, and patient survival. Interdiction of HH-mediated tumor-stroma crosstalk with smoothened (SMO) inhibitors (SHHi) \"primes\" PDAC patient-derived xenograft (PDX) tumors for increased drug delivery by transiently increasing vascular patency/permeability, and thereby macromolecule delivery. However, patient tumor isolates vary in their responsiveness, and responders show co-induction of epithelial-mesenchymal transition (EMT). We aimed to identify the signal derangements responsible for EMT induction and reverse them and devise approaches to stratify SHHi-responsive tumors noninvasively based on c","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-02T11:45:53.952Z","creation":"2025-04-04T12:53:53.281Z"},"accession":"S-EPMC11019863","cross_references":{"pubmed":["38270582"],"doi":["10.1158/1078-0432.ccr-23-0131","10.1158/1078-0432.CCR-23-0131"]}}