biostudies-literatureMancarella SAssociazione Italiana per la Ricerca sul CancroMinistero della Salute331https://www.ebi.ac.uk/biostudies/studies/S-EPMC9703776biostudies-literatureUnknown41(1)<h4>Background</h4>Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant tumor characterized by an intensive desmoplastic reaction due to the exaggerated presence of the extracellular (ECM) matrix components. Liver fibroblasts close to the tumor, activated by transforming growth factor (TGF)-β1 and expressing high levels of α-smooth muscle actin (α-SMA), become cancer-associated fibroblasts (CAFs). CAFs are deputed to produce and secrete ECM components and crosstalk with cancer cells favoring tumor progression and resistance to therapy. Overexpression of Notch signaling is implicated in CCA development and growth. The study aimed to determine the effectiveness of the Notch inhibitor, Crenigacestat, on the surrounding microenvironment of iCCA.<h4>Methods</h4>We investigated CrenigaceJournal of experimental & clinical cancer research : CRCrenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-β inhibition.PMC9703776IG 2020 ID 24815Ricerca Corrente 2022Pizzuto EDituri FMancarella SSerino GChen XArmentano RWang JCalvisi DFGiannelli GGigante IValentini MFfalseCrenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-β inhibition.<h4>Background</h4>Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant tumor characterized by an intensive desmoplastic reaction due to the exaggerated presence of the extracellular (ECM) matrix components. Liver fibroblasts close to the tumor, activated by transforming growth factor (TGF)-β1 and expressing high levels of α-smooth muscle actin (α-SMA), become cancer-associated fibroblasts (CAFs). CAFs are deputed to produce and secrete ECM components and crosstalk with cancer cells favoring tumor progression and resistance to therapy. Overexpression of Notch signaling is implicated in CCA development and growth. The study aimed to determine the effectiveness of the Notch inhibitor, Crenigacestat, on the surrounding microenvironment of iCCA.<h4>Methods</h4>We investigated Crenigace2022-01-01T00:00:00Z2022 Nov2026-05-28T21:26:47.134Z2024-11-21T01:22:54.714ZS-EPMC97037763644382210.1186/s13046-022-02536-6