LAE001 + prednisone + afuresertib

LAE001 + prednisone + afuresertib is a combination therapy under investigation for the treatment of metastatic castration-resistant prostate cancer (mCRPC) and other advanced cancers. **LAE001** is an orally available, non-steroidal, small molecule dual inhibitor of CYP17A1 and CYP11B2 enzymes, which are involved in androgen and aldosterone synthesis. By inhibiting these enzymes, LAE001 reduces androgen production (critical for prostate cancer growth) and aldosterone synthesis, potentially allowing its use without the need for concomitant corticosteroids like prednisone[1][2][3][5]. **Afuresertib** is an oral small molecule pan-AKT kinase inhibitor that targets all three AKT isoforms (AKT1/2/3), disrupting key signaling pathways involved in cell survival, proliferation, metabolism, and resistance to chemotherapy[6][8]. Prednisone is a synthetic glucocorticoid used as supportive care to manage side effects or hormone imbalances during anti-androgen therapies. This combination aims to maximize anti-tumor efficacy by simultaneously blocking androgen signaling (via CYP17A1 inhibition), reducing potential mineralocorticoid-related toxicities (via CYP11B2 inhibition), suppressing AKT-driven tumor growth pathways (via afuresertib), and managing hormonal side effects with prednisone. The regimen has shown promising results in early clinical trials for drug-resistant mCRPC[7].