THE ROLE OF NF-κB AND von HIPPEL-LINDAU PROTEIN IN THE CREATION OF A MOLECULAR PORTRAIT OF KIDNEY CANCERS

DOI: https://doi.org/10.29296/24999490-2019-03-03

L.V. Spirina(1, 2), E.M. Slonimskaya(1, 2), Z.A. Yurmazov(1), E.A. Usynin(1), N.A. Lushnikova(1), N.V. Tarasenko(3, 2), I.V. Kondakova(1) 1-Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Kooperativny street, 5, Tomsk, 634050, Russian Federation; 2-Siberian State Medical University, Moskovsky trakt, 2, Tomsk, 634050, Russian Federation; 3-Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk, Embankment of the Ushayka River, 10, Tomsk, 634050, Russian Federation Е-mail: [email protected]

The review presents data on the role of the nuclear factor NF-κB and the von Hippel-Lindau protein (VHL) in the development of kidney cancer. Chemo- and radioresistance, specific for renal cell carcinoma, represented a significant problem in the treatment of patients. The discovery of the key mechanism of tumor progression was a significant breakthrough for this disease, where surgical approaches prevailed for a long time. The majority of renal cell carcinoma cases is known to be are associated with germ or somatic mutations of the VHL protein, realized through overexpression of the nuclear hypoxia-induced factor (HIF-1) and hyperproduction of vascular endothelial growth factor (VEGF). However, the use of targeted drugs blocking key molecules associated with the angiogenesis fails to increase the number of objective responses in patients. In addition, the role of inflammatory reactions and, in particular, their key mediator, NF-κB, in the oncogenesis of kidney cancer has already been proven. Thus, the concept of a tumor molecular portrait has emerged, which is largely mediated by the production of a number of oncoproteins and oncosuppressors, activating nuclear factors NF-κB and HIF-1. In the development of kidney cancer, the VHL protein is crucial due to the capacity of triggering a cascade of molecular reactions associated with the neoangiogenesis, as well as the regulation of inflammatory responses. Consequently, the determination of the biological features of the tumor is significant in creating the optimal approaches for the personalized treatment of kidney cancer patients.
Keywords: 
kidney cancer, von Hippel–Lindau protein (VHL), NF-κB, HIF-1
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