Trial of RAD001 in Triple Negative Metastatic Breast Cancer

RAD001 is an orally administered cell cycle inhibitor with antitumor activity. RAD001, like
Rapamycin, binds with high affinity to an intracellular immunophilin, FKBP12 and this
complex specifically interacts with the mammalian target of rapamycin (mTOR) protein kinase,
inhibiting downstream events such as the initiation of mRNA translation. RAD001 inhibits the
growth of a wide range of histologically diverse tumor cells. RAD001 is being developed as a
cytostatic agent to delay the time to tumor recurrence/progression or to increase survival
in patients with various malignancies. The compound has good tolerability, a partially
discovered mechanism of action. RAD001 has the ability to arrest cells in the G1 phase, and
the ability to induce apoptosis. RAD001 is being investigated as an anticancer agent based
on its potential to act directly on the tumor cells by inhibiting tumor cell growth and
proliferation through possible inhibition of the PI3/AKT/MTOR pathway.

RAD001 was shown to have activity in human tumor cell lines originating from lung, breast,
prostate, colon, kidney, melanoma and glioblastoma. RAD001 was also shown to have activity
in human pancreatic neuroendocrine cells, where induction of apoptosis was reported, as well
as in acute myeloid leukemia cells, adult T-cell leukemia cells, diffuse large B cell
lymphoma cells, pancreatic tumor cells, ovarian cancer cells, and hepatocellular carcinoma
cells.