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Research on the Resistance Mechanism of Prostate Cancer to BL-B01D1

ABSTRACT: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with limited treatment options following resistance to AR signaling inhibitors. Despite the known roles of EGFR and HER3 in prostate cancer progression, prior therapies targeting this pathway have failed clinically. In this study, we evaluate the therapeutic potential of BL-B01D1, a bispecific antibody–drug conjugate (ADC) targeting EGFR and HER3, in prostate cancer models. BL-B01D1 exhibited potent, target-dependent cytotoxicity across prostate cancer cell lines, xenografts, and patient-derived organoids. Mechanistically, we identified ABCG2 upregulation as a driver of acquired resistance, and pharmacological inhibition of ABCG2 restored drug sensitivity. These findings establish BL-B01D1 as a promising therapeutic strategy in mCRPC and nominate ABCG2 as a potential combination target to overcome resistance.

ORGANISM(S): Mus musculus

PROVIDER: GSE301648 | GEO | 2026/02/10

REPOSITORIES: GEO

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