title: 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.
authors.affiliation: Genetic Service, Cytogenetic Laboratory, Hospital Center of Trás-os-Montes and Alto Douro, Vila Real, Portugal. MLLEITE@chtmad.min-saude.pt.|Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal. MLLEITE@chtmad.min-saude.pt.
authors.forename: R
authors.initials: R
authors.lastname: Pinto-Leite
authors.affiliation: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.|QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal.|Institute for Research and Innovation in Health (I3S), Porto, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Arantes-Rodrigues
authors.affiliation: Health School, University Fernando Pessoa, Porto, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
authors.affiliation: Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal.
authors.forename: P A
authors.initials: PA
authors.lastname: Oliveira
authors.affiliation: Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal.|Health School, University Fernando Pessoa, Porto, Portugal.|Medical Oncology Department, Portuguese Institute of Oncology, Porto, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Santos
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006801:Humans; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D058570:TOR Serine-Threonine Kinases
keywords: Everolimus; Sirolimus; Temsirolimus; Urinary bladder cancer; mTOR