Afinitor (everolimus), approved July 2012, oral

The human epidermal growth factor receptor 2 (HER2), which is encoded by the ErbB2 gene, is a protein that appears on the surface of some breast cancer cells. HER2-negative breast cancers have little or no HER2 protein and are considered to be low-grade cancers. A cancer is called hormone-receptor-positive (or HR+) and the cancer cells, like normal breast cells, may receive signals from the hormone that could promote growth. FKBP-12 is an immunophilin and peptidyl-prolyl cis-trans isomerase, and Everolimus binds to FKBP-12, forming a complex. This complex binds to mTORC1 kinase directly, and inhibits the mTORC1 pathway, leading to inhibition of protein synthesis of the cancer cell.

To treat hormone receptor-positive, HER2-negative breast cancer. Phase 3 trial in patients with hormone-receptor-positive advanced breast cancer showing that the addition of everolimus to endocrine therapy shows improved efficacy [183] [184] .

Afinitor (everolimus), FDA approved May 2011, oral

Autocrine factor such as insulin-like growth factor 1, has been implicated in the proliferation of pancreatic neuroendocrine tumor cells [185] . The growth factor activates both the mTORC1,2 complexes and the network described in Section 3 (see Figure 2). Everolimus inhibits the protein mTOR and thus the mTOR pathway of protein synthesis. Based on the third trial of the key reference, everolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies [185] .

To treat advanced pancreatic neuroendocrine tumors. [186] [187] . See details of Section 3 of this paper.