Howard A. "Skip" Burris, III, MD, chief medical officer and executive director, Drug Development Program, Sarah Cannon Research Institute in Nashville, Tennessee, discusses successful clinical applications for the inhibition of the mammalian target of rapamycin (mTOR) pathway.

Temsirolimus was the first mTOR inhibitor to gain approval for metastatic renal cell carcinoma (RCC). The inhibitors ability to affect the cell cycle, angiogenesis, and proliferation allows it to play multiple roles in the treatment process.

The mTOR agent everolimus (Afinitor), which is also approved for RCC, demonstrated positive results in endocrine cancers. The BOLERO-2 trial demonstrated the efficacy of everolimus for hormone receptor-positive metastatic breast cancer when used in combination with exemestane.

Burris notes that recent studies have shown that blocking more than one pathway is an attractive option, especially for breast cancer. The PI3K/AKT/mTOR pathway plays an important role because the mutation, upregulation and overexpression of PI3K and AKT and the loss of PTEN sets this pathway up as a driver for breast cancer proliferation.

Other pathways work alongside mTOR, including HER2 and hormonal pathways. Dual blockade of mTOR and its neighboring pathways has demonstrated benefits in clinical trials. Burris suggests that blocking the PI3K/AKT/mTOR stream with an mTOR inhibitor is a reasonable opportunity to improve treatment.