Article

EPAS1 Adaptive Loss-of-Function Variants as Germline Determinants of Primary Antiangiogenic TKI Resistance in High-Altitude Hepatocellular Carcinoma: A Translational Pharmacogenomic Study

2026-08-07

Abstract excerpt

<h4>Purpose</h4> Host germline genetic variation as a determinant of tumor drug response remains underexplored. We evaluated whether EPAS1 (HIF-2α) adaptive loss-of-function variants, enriched in high-altitude-adapted populations, predispose HCC to primary antiangiogenic TKI resistance through a HIF-2α/STC2 signaling axis, with implications for TKI selection and belzutifan combination strategies. <h4>Experimental...

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Literature Corpus work: 47760776-7ac5-58ea-a877-dc81b8df596f
DOI: 10.64898/2026.08.05.26358954

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