nelfinavir + temsirolimus

A combination of nelfinavir, an HIV protease inhibitor with anticancer properties, and temsirolimus, an mTOR inhibitor. This combination has been investigated in clinical trials for advanced cancers, including renal cell carcinoma. The combination leverages complementary mechanisms of action. Temsirolimus inhibits mTOR (mammalian target of rapamycin), which controls cell division and when inhibited results in G1 growth arrest in tumor cells. Nelfinavir has multiple potential anticancer mechanisms, including inhibition of proteases involved in protein maturation and folding in the endoplasmic reticulum, which can trigger endoplasmic reticulum stress and the unfolded protein response. Additionally, nelfinavir appears to have weak but broad inhibitory effects on multiple protein kinases that are found upstream of important cancer-related pathways including Akt, MAPK, JNK, NF-κB, mTOR, and focal adhesion pathways.