mTOR inhibitors in urinary bladder cancer

Abstract

Despite the great scientific advances that have been made in cancer treatment, there is still much to do, particularly with regard to urinary bladder cancer. Some of the drugs used in urinary bladder cancer treatment have been in use for more than 30 years and show reduced effectiveness and high recurrence rates. There have been several attempts to find new and more effective drugs, to be used alone or in combination with the drugs already in use, in order to overcome this situation.The biologically important mammalian target of rapamycin (mTOR) pathway is altered in cancer and mTOR inhibitors have raised many expectations as potentially important anticancer drugs. In this article, the authors will review the mTOR pathway and present their experiences of the use of some mTOR inhibitors, sirolimus, everolimus and temsirolimus, in isolation and in conjunction with non-mTOR inhibitors cisplatin and gemcitabine, on urinary bladder tumour cell lines. The non-muscle-invasive cell line, 5637, is the only one that exhibits a small alteration in the mTOR and AKT phosphorylation after rapalogs exposure. Also, there was a small inhibition of cell proliferation. With gemcitabine plus everolimus or temsirolimus, the results were encouraging as a more effective response was noticed with both combinations, especially in the 5637 and T24 cell lines. Cisplatin associated with everolimus or temsirolimus also gave promising results, as an antiproliferative effect was observed when the drugs were associated, in particular on the 5637 and HT1376 cell lines. Everolimus or temsirolimus in conjunction with gemcitabine or cisplatin could have an important role to play in urinary bladder cancer treatment, depending on the tumour grading.

Proteomics analysis of bladder cancer invasion: Targeting EIF3D for therapeutic intervention

“…Additionally, all detected proteins involved in this pathway were up-regulated in MIBC versus NMIBC. Interestingly, eIF2 signaling partially overlaps with the mTOR pathway, which is under investigation in the context of BC, with mTOR inhibitors being tested as potential targets for BC therapeutic intervention [ 49 ]. Given, in addition, the existing interest on protein synthesis as a source of promising anticancer drugs [ 50 ], we shortlisted pathways related to protein synthesis for further investigation, focusing on eIF2 and mTOR signaling.…”

Oncological Impact of M-Tor Inhibitor Immunosuppressive Therapy after Liver Transplantation for Hepatocellular Carcinoma: Review of the Literature

“…In particular, an altered expression of the mTOR pathway have been reported in 40–50% of HCCs, while the activation of the mTOR pathway is related to the presence of less differentiated tumors, earlier recurrence, and worse survival outcomes (Ashworth and Wu, 2014 ). The anticancer activity of mTORi has also been demonstrated in breast cancer, urinary bladder cancer, and kidney cancer (Lee et al, 2015 ; Kajiwara and Masuda, 2016 ; Pinto-Leite et al, 2016 ). In addition, incidence and speed of HCC recurrence in multivariate analysis are related to mTOR signaling activation in a statistically significant fashion (Duvoux and Toso, 2015 ).…”

Cuprous oxide nanoparticles inhibit the growth of cervical carcinoma by inducing autophagy

“…It was found that LC3, the marker of autophagy [ 26 , 27 ], increased in response to treatment with CONPs in a dose- and time-dependent manner. It was also found that CONPs could decrease the expression of p-AKT, p-mTOR, and increase the expression of 4EBP1, which are crucial in the development of cancer [ 28 – 30 ] (Figure 6 ).…”