perifosine + docetaxel

**Perifosine + docetaxel** is an experimental combination therapy investigated primarily for the treatment of advanced or resistant cancers, including platinum- and taxane-resistant or refractory epithelial ovarian cancer. **Perifosine** is an oral synthetic alkylphospholipid and AKT inhibitor targeting the PH domain of AKT, thereby inhibiting the PI3K/AKT signaling pathway involved in cell survival and proliferation. **Docetaxel** is a mitotic inhibitor that acts by stabilizing microtubules and blocking cell division. The rationale for combination is that AKT pathway inhibition (by perifosine) may reverse taxane (docetaxel) resistance. Perifosine's mechanism also affects downstream markers like phosphorylated S6 and can modulate several signaling pathways (including upregulation of BCL2, MGMT, and beta-catenin and downregulation of notch, phosphoSRC, and phosphop38). In phase I clinical studies, perifosine 150 mg orally daily with docetaxel 75 mg/m² IV every 4 weeks was tolerated, but efficacy signals were seen primarily in patients with PI3K pathway activating mutations such as PTEN or PIK3CA[1][3][4].