From the Guidelines
Rapamycin (Sirolimus) has an anti-cancer effect.
Mechanism of Action
The anti-cancer effect of rapamycin is primarily due to its ability to inhibit the mammalian target of rapamycin (mTOR), a key regulator of cell growth and proliferation 1.
Clinical Evidence
Studies have shown that mTOR inhibitors, including rapamycin and its analogs, have been tested in preclinical and early clinical investigations for the treatment of various types of cancer, including hepatocellular carcinoma 1 and endometrial cancer 1.
Specific Cancers
Rapamycin has been found to have a promising role in managing nonmelanocytic skin cancers and Kaposi sarcomas in patients after kidney transplantation, due to its simultaneous immunosuppressive and anti-cancer effects 1.
Ongoing Research
Further research is needed to fully understand the anti-cancer effects of rapamycin and its potential applications in clinical practice, including its use in combination with other targeted therapies and immunotherapies 1.
Key Findings
The use of rapamycin as an anti-cancer agent is supported by its ability to inhibit mTOR signaling, which is often dysregulated in cancer cells, and its potential to enhance the efficacy of other cancer therapies 1.
The FDA Drug Labels for rapamycin (PO) do not address this question.
From the Research
Anti-Cancer Effects of Rapamycin
Rapamycin, also known as Sirolimus, has been shown to have anti-cancer effects in various studies. The key findings are:
- Rapamycin and its derivatives have been found to be promising therapeutic agents with both immunosuppressant and anti-tumor properties 2.
- The anti-cancer effects of rapamycin are mediated through the specific inhibition of the mTOR protein kinase, which serves as part of an evolutionarily conserved signaling pathway that controls the cell cycle in response to changing nutrient levels 2.
- Rapamycin has been found to inhibit tumor growth by halting tumor cell proliferation, inducing tumor cell apoptosis, and suppressing tumor angiogenesis 2, 3.
Mechanism of Action
The mechanism of action of rapamycin's anti-cancer effects involves:
- Inhibition of mTOR complex 1 and suppression of phosphorylation of 4E-BP1, which correlates with the apoptotic effects of high-dose rapamycin treatment 4.
- Dissociation of Raptor from mTORC1, which is required for the apoptotic effect of rapamycin 4.
- Induction of autophagy, which can mediate programmed cell death of cancer cells, especially in hypoxic conditions 5.
Effective Dosing Schedules
The effective dosing schedules of rapamycin for its anti-cancer effects have been investigated, and the findings suggest that:
- Low-level rapamycin dosing is most effective in controlling tumors in mice, with optimal antiangiogenic rapamycin levels being compatible with immunosuppressive doses 3.
- Continuous rapamycin infusion is more effective than bolus dosing in inhibiting tumor growth 3.
Specificity of Rapamycin
The specificity of rapamycin as an mTOR inhibitor has been evaluated, and the findings suggest that:
- Rapamycin has a high specificity towards mTOR, with virtually no changes in mRNA or protein levels in rapamycin-treated cells expressing a rapamycin-resistant mTOR mutant 6.