perifosine + gemcitabine

**Perifosine + gemcitabine** is a combination of two small-molecule anticancer drugs. **Perifosine** is an oral synthetic alkylphospholipid that inhibits signal transduction pathways including the PI3K/Akt pathway. **Gemcitabine** is a nucleoside analog that is incorporated into DNA, causing chain termination and inhibiting DNA synthesis, and is widely used as chemotherapy. The combination has been investigated primarily for **pancreatic ductal adenocarcinoma (PDAC)** and other solid tumors. Preclinical studies show that perifosine can enhance the antitumor efficacy of gemcitabine, especially in tumor cells with high phospho-Akt expression by synergistically inhibiting proliferation, migration, and invasion, as well as promoting apoptosis through upregulation of E-cadherin, activation of caspases, and downregulation of anti-apoptotic factors like Bcl-2 and NF-kB[1]. This combination's efficacy appears to be context-dependent, showing synergism in models with high Akt activation and antagonism in others.