Mammalian target of rapamycin (mTOR) gene polymorphisms exert the major effects on the regulation of transcriptional activity and miRNA binding or splicing, which may be associated with cancer risk by affecting mTOR gene expression.
The mammalian target of rapamycin (mTOR) is an unconventional protein kinase that is centrally involved in the control of cancer cell metabolism, growth and proliferation.
A total of 26 of these miRNAs targeted genes involved in pathways connected to the three main features of SSc and to cancer development including Epidermal growth factor (EGF) receptor, ErbB1 downstream, Sphingosine 1 phosphate receptor 1 (S1P1), Activin receptor-like kinase 1 (ALK1), Endothelins, Ras homolog family member A (RhoA), Class I Phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), p38 mitogen-activated protein kinase (MAPK), Ras-related C3 botulinum toxin substrate 1 (RAC1), Transforming growth factor (TGF)-beta receptor, Myeloid differentiation primary response 88 (MyD88) and Toll-like receptors (TLRs) pathways.
Molecular genetic aberrations in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway are common in human cancers including glioblastoma, yet, novel therapeutic approaches targeting this pathway in glioblastoma have not been successful.
Several studies have shown that the mammalian target of rapamycin (mTOR) inhibitor; everolimus (EV) improves patient survival in several types of cancer.
A key target of PA is the mammalian target of rapamycin (mTOR), a serine-threonine kinase that has been widely implicated in cancer cell survival signals.
Epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) play important roles in tumor growth, which has stimulated efforts toward the design of targeted cancer therapeutics that inhibit their function.
Mammalian target of rapamycin (mTOR) acts as a hub integrating signals from nutrient availability and growth factors and plays central roles in regulating protein synthesis and cell growth, which has been validated as a promising target for cancer therapy.
On multivariable analysis, use of 2 or more immunosuppressant agents (P<.001), older age (P<.001), male sex (P<.001), white race (P<.001), previous malignancy (P<.001), older donor age (P=.003), and white donor race (P=.03) increased de novo malignancy, whereas mammalian target of rapamycin inhibitor use decreased risk (P=.01), driven by a reduction in skin cancer.
It extensively discusses the genetic deregulation of mTOR including amplifications and somatic mutations, mTOR-mediated cell growth promoting signaling, therapeutic targeting of mTOR and the mechanisms of resistance, the role of mTOR in precision medicine and other recent advances in further understanding the role of mTOR in cancer.
This is paralleled by inactivation of the AMPK and activation of the mammalian target of rapamycin (mTOR) C1 signaling pathways, resulting in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) accumulation, induction of DNA damage, and exacerbation of cancer cell aggressiveness, thus contributing to the genomic instability and predisposition to increased tumorigenesis in the diabetic milieu.
In hormone-insensitive prostate (PC3) and breast (MDA-MB-231 and BT-549) cancer cell lines the mTOR inhibitor RAD001 (everolimus) has significantly inhibited SK1 and VEGF expression, while low dose (5 nM) docetaxel had no significant effect.
Inhibition of mTOR complex I (mTORC1) with rapamycin delays aging and increases healthy longevity in laboratory animals and is used clinically at high doses to prevent organ transplant rejection and to treat some forms of cancer.
The ability of rapamycin to inhibit cancer cell proliferation has led to efforts to develop rapamycin and related mTOR inhibitors as anticancer agents.
Seven hundred and fifty-three (753) gastric adenocarcinoma patients and 854 matched healthy subjects were recruited in the cancer association study and 60 tissues were used to test the expression of mTOR.
Here, we discuss the case history of the discovery and properties of an increasingly used chemical probe, the pan-class I PI3K and mammalian target of rapamycin (mTOR) inhibitor PI-103 (a pyridofuropyrimidine), and its very recent evolution into the thienopyrimidine drug GDC-0941, which exhibits excellent oral anticancer activity in preclinical models and is now undergoing phase I clinical trials in cancer patients.
Mammalian target of rapamycin (mTOR) is an evolutionarily conserved protein kinase. mTOR forms two distinct functional multiprotein kinase complexes that mutually phosphorylate different substrates and regulate a wide array of essential cellular processes including translation, transcription and autophagy. mTOR is active in several types of cancer and plays a role in a variety of other serious human diseases, including diabetes, neurodegenerative disorders and polycystic kidney disease.
Rapamycin inhibits mTOR and is effective in preventing kidney transplant rejection, with the additional merits of reduced incidence of malignancies and viral infections.
Mammalian target of rapamycin (mTOR) activation is one of the most frequent events in human malignancies, and is critical for sustaining the self‑renewing ability of cancer stem cells (CSCs); inhibition by rapamycin is an effective and promising strategy in anticancer treatments.