Urothelial carcinoma is the most common type of malignancy in long-term dialysis patients and kidney transplant recipients in Taiwan. mTORCs (mammalian target of rapamycin complexes) and EGF are important in urothelial carcinoma.
Mutations in the B-cell antigen receptor-associated protein CD79B with upregulation of the MTOR pathway were associated with diminished response, but preclinical combination of PIK3CA and PIK3CD inhibitors synergized with ibrutinib to overcome this resistance mechanism, providing opportunity for further targeted therapy of this difficult-to-treat disease.<i>Cancer Discov; 7(9); 940-2.
Genetic variants in the mammalian target of rapamycin (mTOR) gene have become an interesting topic for the study of genetic susceptibility to cancer, but their associations with the risk of gastric cancer have not been fully investigated.
Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk.
Genetic polymorphisms in mTOR gene may be associated with cancer risk and clinical outcomes of cancer patients by affecting mTOR gene expression or its activation.
In addition, the Ras/Raf/mitogen‑activated protein kinase kinase (MEK)/extracellular signal‑regulated kinase (ERK) and phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways are the most commonly dysregulated kinase cascades in human cancer.
Two classes of mTOR inhibitors are currently being evaluated as cancer therapeutics: rapamycin and its analogs, which partially inhibit mTORC1 and in some cell types mTORC2, and the recently described ATP-competitive inhibitors, which inhibit the kinase activity of both complexes.
These include the FKBP12-rapamycin-binding proteins Tor1p, Tor2p, and FRAP, S. pombe rad3, and the product of the ataxia telangiectasia gene, mutations in which lead to genomic instability and predisposition to cancer.
In tuberous sclerosis (TSC)-associated tumors, mutations in the TSC genes lead to aberrant activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. mTORC1 signaling impacts many biological processes including the epithelial-mesenchymal transition (EMT), which is suggested to promote tumor progression and metastasis in various types of cancer.
Newly identified classes of mTOR inhibitors are being developed to block autoimmune diseases and transplant rejections but also to treat obesity, diabetes, and different types of cancer.
Recently, a functional polymorphism (rs2295080 T>G) in the promoter of MTOR has been shown to influence its expression and confer susceptibility to cancer.
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.
Mammalian target of rapamycin (mTOR) inhibitors such as rapamycin have shown modest effects in cancer therapy due in part to the removal of a negative feedback loop leading to the activation of the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling pathway.
The antiproliferative activity of NVP-BEZ235 was superior to the allosteric selective mTOR complex inhibitor everolimus in a panel of 21 cancer cell lines of different origin and mutation status.
Contrarily, the finding for the MTOR gene and breast cancer is biologically plausible because the MTOR protein plays an important role in PI3K/Akt signaling, which is a pathway related to cancer development and cell senescence.
The phosphoinositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway is a frequently hyperactivated pathway in cancer and is important for tumor cell growth and survival.
The phosphoinositide 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) pathway is a critical regulator of cell growth and is frequently hyperactivated in cancer.
Taken together, our results revealed that the MAP3K7-mTOR axis might promote tumorigenesis and malignancy, which provides a potential marker or therapeutic target for HCC patients.