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Review
. 2021 Feb 9;22(4):1743.
doi: 10.3390/ijms22041743.

The Role of mTOR Signaling as a Therapeutic Target in Cancer

Nadezhda V Popova  1 , Manfred Jücker  2
Affiliations
Review

The Role of mTOR Signaling as a Therapeutic Target in Cancer

Nadezhda V Popova et al. Int J Mol Sci. .

Abstract

The aim of this review was to summarize current available information about the role of phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling in cancer as a potential target for new therapy options. The mTOR and PI3K/AKT/mTORC1 (mTOR complex 1) signaling are critical for the regulation of many fundamental cell processes including protein synthesis, cell growth, metabolism, survival, catabolism, and autophagy, and deregulated mTOR signaling is implicated in cancer, metabolic dysregulation, and the aging process. In this review, we summarize the information about the structure and function of the mTOR pathway and discuss the mechanisms of its deregulation in human cancers including genetic alterations of PI3K/AKT/mTOR pathway components. We also present recent data regarding the PI3K/AKT/mTOR inhibitors in clinical studies and the treatment of cancer, as well the attendant problems of resistance and adverse effects.

Keywords: AKT; PI3K; cancer; mTOR; mutation; therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Domain structure of mTOR and components of mTORC1 and mTORC2. DEPTOR, DEP domain-containing mTOR-interacting protein; FAT, FRAP/ATM/TRRAP; FATC, FRAP/ATM/TRRAP/Carboxy terminal; FKBP-12, FK506-binding protein-12; FRB, FKBP12-rapamycin-binding; HEAT, Huntingtin/Elongation factor 3/A subunit of protein phosphatase-2A/TOR1; mLST8, mammalian lethal with SEC13 protein 8; mSIN1, mammalian stress-activated protein kinase interacting protein 1; mTOR, mechanistic target of rapamycin; mTORC1, mTOR complex 1; mTORC2, mTOR complex 2; PRAS40, proline-rich AKT substrate 40 kDa; Protor, protein observed with RICTOR; RAPTOR, regulatory-associated protein of mTOR; RICTOR, rapamycin-insensitive companion of mTOR. The picture was modified from [53].
Figure 2
Figure 2
The overview of phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway and inhibitors.
See this image and copyright information in PMC

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