perifosine + temsirolimus

Perifosine + temsirolimus is a combination of two investigational small molecule drugs targeting the PI3K/AKT/mTOR signaling pathway, which is frequently dysregulated in various cancers. Perifosine acts as an AKT inhibitor, blocking upstream signaling in the PI3K pathway and also affecting other cascades such as RAS. Temsirolimus is an mTOR inhibitor that binds to FKBP-12 and inhibits mTOR activity, leading to cell cycle arrest in G1 phase and reduced tumor angiogenesis by decreasing VEGF synthesis. The combination has shown synergistic effects in preclinical models of glioblastoma and pediatric gliomas, resulting in enhanced tumor necrosis and proliferation arrest compared to either agent alone. This regimen has been investigated primarily for recurrent or refractory solid tumors including gliomas[3][6].