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We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for the first time, we applied OncoFinder for normal and cancerous tissues of the human bladder to identify biomarkers of bladder cancer. Using Illumina HT12v4 microarrays, we profiled gene expression in 17 cancer and seven non-cancerous bladder tissue samples. These experiments were done in two independent laboratories located in Russia and Canada. We calculated pathway activation strength values for the investigated transcriptomes and identified signaling pathways that were regulated differently in bladder cancer (BC) tissues compared with normal controls. We found, for both experimental datasets, 44 signaling pathways that serve as excellent new biomarkers of BC, supported by high area under the curve (AUC) values. We conclude that the OncoFinder approach is highly efficient in finding new biomarkers for cancer. These markers are mathematical functions involving multiple gene products, which distinguishes them from “traditional” expression biomarkers that only assess concentrations of single genes.

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The standards of treatment for metastatic renal cell carcinoma (mRCC) have changed significantly from unsuccessful attempts of radiation and cytostatic therapy to the encouraging results of targeted therapy and specific immunotherapy. Sunitinib has got into the practice in 2006, and now it`s one of the most studied and approved. Sunitinib is one of the first oral targeted drugs for RCC. It affects such receptors as VEGFR1, 2, 3; PDGFR, FGFR, c-KIT, and RET, which take part in the pathologic angiogenesis, tumor growth, and metastasizing. Moreover, sunitinib stimulates the growth and development of lymphatic vessels, that deliver immunocytes to the tumor. The advantage of sunitinib over non-specific immunotherapy has been proven by Motzer et al. The randomized trials COMPARZ, RECORD-3, and SWITCH have confirmed that sunitinib is more effective than several targeted drugs (pazopanib, everolimus, and sorafenib respectively) as the first line of treatment for mRCC. The randomized trial of the 3rd phase CARMENA has demonstrated the importance of sunitinib monotherapy for mRCC of intermediate and poor prognosis. In general, sunitinib has been proven to be an effective first-line drug for mRCC, as it`s evidenced in the comprehensive metaanalysis of real-world data and randomized controlled trials published between 2000 and 2017. Nowadays, despite the success of the immunotherapeutic direction, tyrosine kinase inhibitors, and particularly sunitinib, rightfully remain the standard for mRCC of favourable prognosis, the treatment option for worse prognosis in case of contraindications for other methods of therapy, and it` s also used in subsequent therapy lines.

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