Репозиторий Университета

© 2018, Pleiades Publishing, Ltd. Fibroblast growth factor (FGF) plays an important role in human embryogenesis, angiogenesis, cell proliferation, and differentiation. Carcinogenesis is accompanied by aberrant constitutive activation of FGF receptors (FGFRs) resulting from missense mutation in the FGFR1-4 genes, generation of chimeric oncogenes, FGFR1-4 gene amplification, alternative splicing shift toward formation of mesenchymal FGFR isoforms, and FGFR overexpression. Altogether, these alterations contribute to auto-and paracrine stimulation of cancer cells and neoangiogenesis. Certain missense mutations are found at a high rate in urinary bladder cancer and can be used for non-invasive cancer recurrence diagnostics by analyzing urine cell pellet DNA. Chimeric FGFR1/3 and amplified FGFR1/2 genes can predict cell response to the targeted therapy in various oncological diseases. In recent years, high-throughput sequencing has been used to analyze exomes of virtually all human tumors, which allowed to construct phylogenetic trees of clonal cancer evolution with special emphasis on driver mutations in FGFR1-4 genes. At present, FGFR blockers, such as multi-kinase inhibitors, specific FGFR inhibitors, and FGF ligand traps are being tested in clinical trials. In this review, we discuss current data on the functioning of the FGFR family proteins in both normal and cancer cells, mutations in the FGFR1-4 genes, and mechanisms underlying their oncogenic potential, which might be interesting to a broad range of scientists searching for specific tumor markers and targeted anti-cancer drugs.

© 2018 ABC-press Publishing House. All rights reserved. Bladder cancer (BC) is represented by non-muscle-invasive forms at the stage Ta, T1, CIS (NMBC) in 75 % of cases. The gold standard of treatment of NMBC patients is transurethral resection, but its implementation does not always allow the patient to be relieved of the recurrence of the disease. In this regard, patients with a low risk of progression after transurethral resection are administered by intravesical chemotherapy, with high risk (T1G2/3) – using instillation with BCG (Bacillus Calmette–Guerin) vaccine. Searching of NMBC markers for laboratory diagnostics, which would help to determine sensitivity or resistance to the planned type of adjuvant therapy remains an actual problem. The data published mainly in the last 5–7 years about genetic predictors of the response to adjuvant chemotherapy and, to a greater extent, immunotherapy with BCG vaccine, are reviewed in this work. Allele combinations in the genes involved in immune response, xenobiotic biotransformation and other loci that are associated with the response to the adjuvant NMBC therapy in meta-analyzes are systematized. Also, expression profiles of mRNA, microRNA and proteins, as well as panels of methylated loci associated with the effectiveness of chemotherapy and immunotherapy of NMBC are considered. It was demonstrated that the somatic mutations sequencing in the primary tumor and the total mutational load using high-throughput sequencing technologies (NGS) identified a number of potential prognostic markers. Perhaps, the mutational load will be more widely used as a highly informative predictor of immunotherapeutic effect in BC: BCG therapy of NMBC and BC targeted therapy using the inhibitors of immune control points, after the standardization of the analysis. This review is intended to oncologists, geneticists, molecular biologists, urologists, pathologists and other specialists working in the field of molecular genetics in oncological urology.