perifosine + trastuzumab

**Perifosine + trastuzumab** is an experimental drug combination consisting of perifosine, an oral alkylphospholipid small molecule, and trastuzumab, a monoclonal antibody targeting HER2 (human epidermal growth factor receptor 2). Perifosine acts mainly by inhibiting the Akt pathway, interfering with cancer cell survival and proliferation, while trastuzumab binds to the extracellular domain of the HER2 receptor, blocking downstream signaling and mediating antibody-dependent cellular cytotoxicity (ADCC). This combination has been investigated primarily in HER2-positive cancers, particularly breast cancer, including cases resistant to trastuzumab alone. The rationale for the combination is that perifosine may block compensatory pro-survival signaling (such as via PI3K/Akt) that underlies resistance to trastuzumab, thereby enhancing anti-tumor efficacy.