Somatic mutation profiling and functioning of intracellular signaling pathways at various stages of bladder cancer and their significance for targeted therapy

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DOI: 10.29188/2222-8543-2020-12-1-42-51

Sergienko S.A., Mihaylenko D.S., Safronova N.Yu., Efremov G.D., Kaprin A.D., Alekseev B.Ya.
№1 2020

Introduction. Bladdercancer (BC) represents one of the most frequent disease in the structure of morbidity and mortality among malignant neoplasms in human. At the moment, there is a large amount of experimental data about the molecular genetic alterations those occurring in carcinogenesis of BC, but only a few of them are considered as potential predictors of the response to therapy, suitable for using in clinical practice. Many studies underlying BC is a genetically heterogeneous disease. Correlation of various molecular genetic subtypes with clinical and morphological data could be implemented to possible prediction of the BC prognosis and determination of the most effective personalized treatment options.

Purpose of the study. Analysis and summarization of actual studies about molecular genetic changes at the DNA and RNA sequences, and their prognostic significance for patients with BC.

Materials and methods. We used data about genetic alterations in BC and diagnostic test systems published in the PubMed, Elibrary.ru databases, as well as websites of several professional associations for writing this review. Based on the relevance of data, reliability of the sources, impact factors of journals 40 articles in peer-reviewed journals and one guide were studied during the preparation of the review.

The main part. Analysis ofscientific and technical information published overthe past 5 yearswas performed. We have identified three signaling pathways and about ten genes that are their components, mutations in which are characteristic of the main forms of BC: non-muscular- and muscle-invasive. Together with the sequencing data of tumor exomes, expression and immunohistochemical profiles these molecular genetic characteristics made it possible to improve the classification of BC and isolate new molecular subtypes. Various BC molecular subtypes are associated with prognosis, overall survival, the effectiveness of chemo- and targeted therapy, including immune control points inhibitors.

Conclusion. Certain molecular genetic alterations are already included in diagnostic and prognostic test systems (FGFR3 and TERT mutations, a number of immunohistochemical markers), but the vast majority of somatic mutations and genes expression are considered only as a starting point for finding new targeted drugs or prognostic markers. The review is aimed for urologists, oncologists, laboratory geneticists and specialists in related professions.

Conflict of interest. The authors declare no conflict of interest.

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