From the Guidelines
The mammalian target of rapamycin (mTOR) pathway plays a crucial role in regulating cell growth, proliferation, metabolism, and survival, and its dysregulation is implicated in various diseases, including cancer, diabetes, and neurological disorders, making it an important therapeutic target. The mTOR pathway integrates both intracellular and extracellular signals to control major cellular processes, and it functions as a serine/threonine protein kinase that exists in two distinct complexes: mTORC1 and mTORC2. mTORC1 primarily regulates protein synthesis, cell growth, and metabolism by phosphorylating downstream targets like S6K and 4E-BP1, while mTORC2 influences cell survival, cytoskeletal organization, and metabolism through the phosphorylation of proteins such as Akt 1.
Some of the key points to consider when targeting the mTOR pathway include:
- The use of mTOR inhibitors, such as sirolimus and everolimus, which have been shown to be effective in preventing rejection and improving outcomes in patients undergoing liver transplantation 1.
- The importance of monitoring and managing the side effects of mTOR inhibitors, such as hyperlipidemia, thrombocytopenia, and renal dysfunction 1.
- The potential benefits of using combination regimens, such as tacrolimus and mycophenolate mofetil, to reduce the risk of rejection and improve outcomes in patients undergoing liver transplantation 1.
In terms of specific treatment recommendations, the use of everolimus-based regimens has been shown to be effective in improving renal function and reducing the risk of rejection in patients undergoing liver transplantation. However, the optimal dosing and duration of treatment with mTOR inhibitors remains unclear, and further studies are needed to determine the best approach for individual patients 1. Additionally, the use of sirolimus should be avoided during the first month post-transplant, and patients in poor clinical condition and/or requiring prolonged intensive care stay post-transplantation should be maintained on lower immunosuppressive doses than those recommended above 1.
Overall, the mTOR pathway is a critical target for the development of new therapies for a range of diseases, and further research is needed to fully understand its role in regulating cellular processes and to develop effective and safe treatments for patients.
From the FDA Drug Label
The mTOR pathway is dysregulated in several human cancers and in tuberous sclerosis complex (TSC) Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation with mTOR complex 1 (mTORC1) and thus inhibition of mTOR kinase activity. Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds to an intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTOR that controls cell division.
The mammalian target of rapamycin (mTOR) pathway does play a role in several human cancers and in tuberous sclerosis complex (TSC). It is involved in cell division and is dysregulated in these conditions.
- Inhibition of the mTOR pathway can reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies.
- mTOR inhibitors, such as everolimus and temsirolimus, bind to an intracellular protein (FKBP-12) and inhibit the activity of mTOR, which controls cell division 2 3.
From the Research
Mammalian Target of Rapamycin Pathway
The mammalian target of rapamycin (mTOR) pathway is a signaling kinase that plays a crucial role in various aspects of cellular life, including:
- Cell growth and proliferation
- Development and memory
- Longevity and angiogenesis
- Autophagy and immune responses 4 The mTOR pathway consists of two distinct complexes, mTORC1 and mTORC2, which are activated by diverse mitogens, growth factors, and nutrients.
Role of mTOR in Human Health and Disease
The mTOR signaling pathway is involved in maintaining cellular homeostasis and is implicated in various diseases, including:
- Cancer: dysregulation of the mTOR pathway is frequently observed in various cancers, such as renal cell carcinoma 5, 6, 7
- Neurological diseases: emerging evidence suggests that the mTOR pathway plays a role in neurological diseases, such as aging and neurodegenerative disorders 8
- Genetic disorders: the mTOR pathway is also implicated in genetic disorders, such as tuberous sclerosis complex and cystic kidney disease 4
Therapeutic Targeting of mTOR
The mTOR pathway is a potential therapeutic target for various diseases, including cancer and neurological disorders. Several mTOR inhibitors, such as temsirolimus and everolimus, have shown promising clinical activity in advanced renal cell carcinoma 5, 6. However, resistance to these inhibitors can occur due to the complexity of the PI3-K/Akt/mTOR pathway 6. Further research is needed to develop novel therapeutic agents and combination therapies that can effectively target the mTOR pathway.