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    Association details:
    Biomarker:EPAS1 S304M
    Cancer:Clear Cell Renal Cell Carcinoma
    Drug:Welireg (belzutifan) (HIF-2α inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: D – Preclinical
    Source:
    AUA 2023
    Title:

    MP04-12: Pharmacological inhibition of the molecular chaperone Hsp70 overcomes Belzutifan resistance in ccRCC

    Published date:
    03/31/2023
    Excerpt:
    Utilizing previously characterized Belzutifan resistant HIF2a-S304M and -G323E mutants we demonstrated that treating ccRCC cells with Hsp70 inhibitor JG-98 leads to mutant-HIF2a degradation, therefore overcoming Belzutifan resistance….treatment with an Hsp70 inhibitor could potentially be used in the clinic to overcome resistance to Belzutifan in patients with VHL disease and ccRCC.
    Secondary therapy:
    HSP70 inhibitor