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Modulation of Mammalian Target of Rapamycin Signal Machinery in Human Cancer

Thekkuttuparambil A. Ajith1 , Thekkuttuparambil A. Ajith1

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Indian Journal of Cancer Education and Research 3(1):p 17-25, Jan-Jun 2015. | DOI: DOI: https://dx.doi.org/10.21088/ijcer.2321.9815.3115.3

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Abstract

 Mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, regulates cellular process such as growth, proliferation, motility and survival which are mediated through regulating the transcription and protein synthesis. mTOR is the catalytic subunit of two structurally distinct complexes. mTORC1–a master regulator of cell growth and metabolism and mTORC2 is involved in the cytoskeleton organization. Both these complexes are localized to different sub-cellular compartments, thus affecting their activation and function. Though the mTOR signaling has physiological function in cells, an elevated mTOR signaling has been found in many human cancers. Since deregulation has been observed in the mTOR signaling pathway, overwhelming research on this complex machinery has developed inhibitors to inhibit human cancer. Some of them such as temsirolimus, everolimus, are beginning to use in the treatment of cancer. Natural inhibitors of mTOR are found to be effective in cell cultures but none of them is proved to be effective in clinical use. Hence, it will be noteworthy to discuss the physiological importance as well as pathological impact of this signal machinery. This review discusses the physiological role of mTOR, its regulation, involvement in human cancer and pharmacological inhibitors for modulating mTOR activity in cancer. 

Key words: Mammalian Target of Rapamycin; Serine/Threonine Protein Kinase; AMP Dependent Protein Kinase; Protein Kinase B; Phosphatidylinositol 3-Kinase; Temsirolimus; Everolimus.

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DOI: DOI: https://dx.doi.org/10.21088/ijcer.2321.9815.3115.3

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