The mammalian target of rapamycin (mTOR) and associated phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway is commonly up-regulated in cancer, including bladder cancer. mTOR complex 2 (mTORC2) is a major regulator of bladder cancer cell migration and invasion, but the mechanisms by which mTORC2 regulates these processes are unclear.
To address the translational relevance of these findings, the effects of the mTOR complex 1 (mTORC1) inhibitor, rapamycin, on tumor and T cells were monitored in patients undergoing cystectomy for bladder cancer.
Although mechanistic target of rapamycin (mTOR) inhibitors, such as temsirolimus, show promise in treating bladder cancer, acquired resistance often hampers efficacy.
These effects may be due to the puerarin-induced downregulation of proteins in the mTOR/p70S6K signaling pathway, and the present study may provide the experimental basis for puerarin to be considered as a promising novel anti-tumor drug for the treatment of bladder cancer.
Our findings suggested that OA induced protective autophagy through AMPK-mTOR-ULK1 signaling pathway in bladder cancer cells and OA in combination with autophagy inhibitor might be a novel alternative for the treatment of bladder cancer.
Here we focused on mechanistic target of rapamycin (mTOR) inhibition as a chemotherapeutic strategy and characterized the expression profile of mTOR signaling targets in representative bladder cancer cell lines from basal, luminal, and either basal/luminal ("non-type") molecular subtypes.
We thus hypothesized that the use of autophagy inhibitor in combination with mTOR inhibition improves the cytotoxicity of mTOR inhibitors in bladder cancer.
Alterations in the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway are frequent in urothelial bladder cancer (BLCA) and thus provide a potential target for novel therapeutic strategies.
Bioinformatic analysis showed that the mTOR gene was a direct target of miR-100. siRNA-mediated mTOR knockdown phenocopied the effect of miR-100 in bladder cancer cell lines.
Our results provide the first strong evidence that physical activity, energy intake, and genetic variants in the mTOR pathway jointly influence bladder cancer susceptibility and that these results have implications for bladder cancer prevention.
Our integrated analyses of mouse and human bladder cancer provide a rationale for investigating mTOR inhibition for treatment of patients with invasive disease.