Repurposed Acarbose Targets Nidogen-1 to Remodel the Tumor Stroma and Suppress Portal Vein Tumor Thrombus in Hepatocellular Carcinoma - PubMed
3 hours ago
- #Drug Repurposing
- #Tumor Microenvironment
- #Hepatocellular Carcinoma
- Portal vein tumor thrombus (PVTT) is a lethal complication of hepatocellular carcinoma (HCC) with poorly understood molecular mechanisms.
- Multi-omics analysis of 99 specimens from 47 patients revealed intratumoral heterogeneity and enrichment of myofibroblast-like cancer-associated fibroblasts (myCAFs).
- Nidogen-1 (NID1) was identified as a stromal driver of immune barriers in PVTT cores, linked to impaired antitumor immunity.
- Acarbose, an FDA-approved drug, was repurposed to inhibit the NID1 axis, disrupting myCAF-mediated immune barriers and suppressing PVTT progression.
- Acarbose showed synergy with anti-PD-1 therapy in preclinical models and was associated with lower PVTT incidence in a clinical cohort of 810 HCC patients.
- The study highlights drug repurposing as a strategy to improve outcomes in HCC with PVTT.