Identification of genes as potential targets for therapy of neurogenic tumors
Malignant neurogenic tumors are one of the main causes of death in cancer patients in Russia and worldwide. Among neurogenic neoplasms, glioblastoma (tumor of the central nervous system) and neuroblastoma (tumor of peripheral nerve cells, often extra-organic) are particularly aggressive. These tumors are diagnosed in children and young adults; comprehensive treatment remains ineffective. The most important biological feature of neurogenic tumors is high heterogeneity. In fact, glioblastoma (glioblastoma multiforme) and neuroblastoma are nosological units that unite very diverse neoplasms, common for which is a tissue origin - glia of the hemispheric cortex or neurons of the peripheral nervous system. Therefore, it is difficult - and hardly possible - to propose a single therapeutic target: in contrast to tumors with the predominance of a single pathogenetic mechanism (for example, chronic myeloid leukemia caused by the chimeric gene Bcr-Abl), the nosological units "glioblastoma" and "neuroblastoma" are heterogeneous: the specific molecular mechanisms, morphological structure and clinical manifestations of individual forms of these tumors are extremely diverse. The reasons for this diversity should be sought in disorders of certain biologic processes. In glioblastoma and neuroblastoma, there is a disorder of MYCN oncogene copy number, which indicates a weakened control of genome stability, a characteristic feature of tumor cells. Equally important is the widespread deregulation of gene expression. Thus, the phenotypic diversity of neurogenic tumors is based on transcription disorders inherent specifically to neoplasms of childhood and young adulthood. Thus, the problem of identifying the mechanisms of gene transcription disorders in neurogenic tumors is urgent to deepen knowledge about the pathogenesis of these neoplasms and rational design of target-directed drugs. The project is aimed at studying a fundamental biological process - transcription of genes whose products are important for cell viability of neurogenic tumors - glioblastoma and neuroblastoma. The practical aspect, which is a consequence of obtaining fundamental knowledge, is the identification of new targets for drug therapy of these tumors, the impact on which (with the help of chemical tools identified in the project) is important for improving treatment results. For the first time, a systematic study of 5 super-target genes whose products are important for the viability of glioblastoma and neuroblastoma cells (stable cell lines and primary cultures) in comparison with MYCN oncogene status (reference) is planned: MYCN copy number and mRNA levels of super-target genes. For the first time, the primary structure of the regulatory regions of super target genes will be analyzed and transcript levels will be compared with DNA sequencing results. For the first time, the most important super-target genes whose inactivation is lethal for glioblastoma and neuroblastoma will be validated. For the first time, the clinical role of super-target gene abnormalities in glioblastoma and neuroblastoma biopsy specimens will be revealed: frequency in different clinical and morphological variants, comparison with the course of the disease and response to drug treatment.
January 6, 2024 December 31, 2026
List of publications
- (2025). Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma. Nat Commun 16 (1), 471
- (2024). Evaluation of nicotinic acetylcholine receptor subunit expression levels for the improvement of diagnostic approaches and treatment in endometrial hyperplasia and cancer. Akush Ginekol (Mosk) 2024 (12), 108–116
- (2025). Combined Effects of Senexin B and Antitumor Agents on Neuroblastoma and Glioblastoma Cell Lines. Russ. J. Bioorganic Chem. 51 (3), 1279–1286
- (2025). Targeting transcription in neuroblastoma: focus on the Core regulatory circuit. Expert Opin Ther Targets , 1–17
- (2025). Microenvironment of Solid Tumors. Front Biosci (Landmark Ed) 30 (9), 36940
- (2025). Saying “Yes” to NONO: A Therapeutic Target for Neuroblastoma and Beyond. Cancers (Basel) 17 (19), 3228
- (2025). Development of an Experimental Intracranial PDX Model of Human Glioblastoma in NSG Mice. Russ. J. Bioorganic Chem. 51 (5), 2034–2040
- (2025). Influence of Cultivation Conditions on Expression of Transcription Factor Genes in Glioblastoma Cells. Russ. J. Bioorganic Chem. 51 (5), 1962–1969

