Latest research on RAD001

Everolimus is a derivative of Rapamycin (sirolimus), and works similarly to Rapamycin as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. In a similar fashion to other mTOR inhibitors Everolimus' effect is solely on the mTORC1 protein and not on the mTORC2 protein.

RAD001 dosage

As reported in previous studies10, the pan-PI3K inhibitor GDC0941 and the mTOR inhibitor RAD001 significantly suppressed the increased colony formation arising from Pten deletion in a dose-dependent manner (Fig. 5a). [source, 2015]
Eribulin alone, or combined with RAD001, a mTOR inhibitor, showed cell growth inhibition in triple-negative breast cancer and HER2 cell lines, dose-related inhibition of Akt activation, significant synergistic growth inhibition with combination treatment, and reversal of the pAkt feedback response with mTOR inactivation [24]. [source, 2015]
As shown in Figure 2C, treatment of A549 cells with a gradient of concentrations of RAD001 determined that RAD001 decreased 4EBP1 phosphorylation in a dose-dependent manner, indicating that it effectively inhibited mTOR activity. [source, 2015]
For the nine patient samples in which drug effects were evaluated by cell numbers after the longest drug exposure, usually 3 weeks, a mean of 31%+/−6% (SE) of tumor cells remained after treatment with the Mirk kinase inhibitor EHT5372, a mean of 46%+/−10% remained after treatment with the elevated dosage of Cisplatin, a mean of 38%+/−14% remained after treatment with RAD001, and a mean of 9%+/−2% of tumor cells remained after concurrent treatment with the Mirk kinase inhibitor and the mTOR inhibitor RAD001(Fig. 4A). [source, 2014]
EHT5372 increased ROS levels in a dose-dependent manner, while RAD001 did not, with the amount of ROS in the RAD001 treated cells identical to that in untreated cells (Fig.4C). [source, 2014]
Our observations further support that lower dose of mTOR inhibitor (i.e. RAD001) can achieve full target inhibition when combined with an allosteric Akt inhibitor (i.e. MK-2206). [source, 2014]
Here, we also observed a partial inhibition of mTOR signaling by low-dose of RAD001 alone, however, the combination with MK-2206 caused an enhanced inhibitory effect on mTOR activation. [source, 2014]
RAD001 was administered orally twice a week for 4.5 weeks, and a suboptimal dose of 177Lu-DOTATATE (leaving room for additional effect of RAD001) was given once. [source, 2014]
For these two doses, no dose dependence of RAD001 was found (Table 2). [source, 2014]
We earlier hypothesized multiple reasons for the occurrence of metastases: the twice-weekly dose regimen instead of daily dosing as is applied in clinical therapy, effects of RAD001 on the immune system and/or tumor microenvironment, or the discontinuation of RAD001 treatment at 4.5 weeks after start of treatment. [source, 2014]