Introduction. Immunoenzyme assay of biochemical markers is one of the most important methods for examination of pa- tients with neuroendocrine tumors (NETs). Along with the generally accepted NET marker chromogranin A (CgA), another member of the granin family, chromogranin B (CgB), can serve as a complementary marker.

Objectives. Analysis of CgB as an additional to CgA biochemical marker in the blood serum of patients with gastric and pancreatic neuroendocrine tumors.

Materials and methods. We examined 79 patients with gastic (n = 14) and pancretic (n = 65) NETS, and 42 particularly healthy people, who were included in the control group. CgB and CgA were determined with ELISA method using the Human Chromogranin B (USCN, China) and Chromogranin A NEOLISA (Eurodiagnostica, Sweden) test systems.

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Results. CgB levels in gastric and pancreatic NETs were significantly higher than in control group. CgB concentrations were independent of tumor spread and its biological activity. ROC analysis in common group of NETs relative to control group showed AUC for CgB = 0.869 and for CgA AUC = 0.82. According to results in common group of NET patients when used isolated, CgA and CgB have comparable diagnostic sensitivity, which increases in complex use to 82.5 %. In the group of NET patients with low levels of CgA (<100 ng/ml), an increase in CgB concentration above the cut-off level (>15.7 ng/ml) was observed in 53.6 % of cases.

Conclusion. The combination of CgB and CgA in gastric and pancreatic NETs could increase the diagnostic efficacy of bio- chemical diagnostics. The received data confirms the significance of CgB as a complementary biomarker of NETs.

Introduction. Epstein–Barr virus (EBV) is equally widespread in the endemic and non-endemic world regions for nasopharyngeal cancer (NPC). High incidence of NPC in endemic countries and low in non-endemic countries suggest there are different mechanisms and conditions for tumor occurrence and, possibly, different clinical significance of EBV-associated markers. However, significance of these markers for determining NPC in non-endemic regions is still poorly understood. Objective – to determine clinical significance of titers of IgG/IgA antibodies to EBV capsid antigen and concentrations of the viral DNA in patients’ blood plasma as diagnostic and monitoring markers for NPC in a non-endemic region of Russia. Materials and methods. Titers of EB-specific antibodies were determined by indirect immunofluorescence, and concentration of the viral DNA in plasma was measured using a quantitative polymerase chain reaction in real time. Study group included patients with NPC (n = 96), and control group – blood donors (n = 171) and patients with other head and neck tumors (n = 33).
Results. Titers of IgG/IgA antibodies to EBV capsid antigen, being an important diagnostic marker of nasopharyngeal cancer, did not always correlate with patients’ clinical condition. Humoral response to emerging events often delayed due to inertia of the immune system. Concentration of EBV DNA in patients’ blood plasma clearly reflected the dynamics of the pathological process: it decreased to background values in remission and increased while the disease progressed. In contrast to endemic regions, we did not find any correlation between the studied EBV markers and clinical manifestations of the disease, evaluated in accordance with the TNM classification (Tumor, Nodus and Metastasis).
Conclusion. In non-endemic countries, such as Russia, serological and molecular markers of EBV can be successfully used for the primary diagnosis of NPC. However, for the disease monitoring, it is preferable to use the value of the concentrations of circulating EBV DNA, which, in contrast to the values of IgG/IgA antibody titers to VCA EBV, more accurately reflect the patient’s clinical condition.

The review article presents data on somatic inactivation of NF1 gene as a cause of sporadic malignant neoplasms. The re- lationship between the features of specific tumors in neurofibromatosis type 1 and specific types of sporadic neoplasms, in which mutations in NF1 gene are found, are presented. Evidence for the role of somatic mutations in NF1 gene in the development of chemoresistance in melanoma, neuroblastoma, ovarian and breast cancer, and lung cancer is described (only if there are no mutations of known protooncogenes). To overcome the resistance of these neoplasms, inhibitors of mitogen-activated protein kinase have been proposed, the effectiveness of which has been proven in the treatment of plexiform neurofibromas. The review presents evidence of the relationship between NF1 and microRNA, which can be used for targeted therapy of both neurofibromatosis type 1 and sporadic neoplasms with mutations of this gene. Prospects for gene therapy of these diseases are considered.

Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy have become one of the key approaches in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Evaluation of level of PD-L1 (ligand of the programmed cell death receptor 1) expression on tumor cells using immunohistochemistry is the only approved option for determining the indications of ICIs in this group of patients. However, despite high level of PD-L1 expression, up to 80 % of patients do not respond to therapy due to the presence of primary or acquired resistance, which determines the limited effectiveness of ICI. In addition, 8–17 % of PD-L1-negative patients with NSCLC are also able to respond to ICIs. The limitation of this marker is that it does not allow assessing both intratumoral and systemic immune status. It is necessary to search for additional predictive markers to improve the accuracy of the selection of candidates for immunotherapy, which will avoid costs, wasted time, and a high risk of immune-related adverse events in potentially unresponsive patients. The attention of researchers is devoted to circulating markers in peripheral blood, as a non-invasive alternative to biopsy for predicting and monitoring the response. This review focuses on the most promising immunological markers in peripheral blood as potential predictors of response to ICIs in patients with advanced NSCLC.

Primary or secondary resistance is an important problem when treating any type of tumor. It is often associated with changes in target genes’ functioning. This raises the question of understanding functional intracellular interactions of genes and proteins in oncological processes and therapeutic resistance occurring. When searching target proteins of targeted therapy, it is necessary to identify biomolecules, participating in cell signaling life, which differ significantly in normal and oncological processes and interact with a large number of pathways. It is also important that these biomolecules are not an artifact of tumor therapy or cell line cultivation, and that it is possible to influence them directly, obtaining complex effect. In addition, it is important to study changes occurring during therapy with the biomolecules, which include proto-oncogene of SRC family kinase LYN and gene of the estrogen receptor α ESR1. All these factors may help to overcome the emerging resistance.
Objective – to study the way genes of SRC kinase LYN and estrogen receptor α ESR1 influence oncological processes and occurrence of therapeutic resistance.

Glioblastoma multiforme is the most common and malignant primary tumor of the central nervous system. Despite the existing modern complex therapy and advances in the study of molecular genetic changes in this tumor, the prognosis for patients with glioblastoma is one of the most unfavorable in oncology. This overview reviews existing therapeutic agents and clinical studies of potential drugs for the treatment of patients with glioblastoma multiforme.
Next-generation sequencing has become firmly established in the clinical practice of oncologists and allows detecting gene mutations in tumor cells, some of which can serve as targets for therapy. Glioblastoma is characterized by a large number of potentially targeted molecular genetic disorders. As in the case of other solid tumors, targeted and immunotherapy for glioblastomas is being actively studied, including the combination of drugs with physical methods of exposure. 
To date, new treatment methods of glioblastoma, including antiangiogenic therapy, immunotherapy, oncolytic viral therapy and gene therapy still have uncertain or very modest clinical results. There are many reasons for the lack of progress in the treatment of glioblastoma – from the banal inability of most molecules to overcome the blood-brain barrier to the wide genetic heterogeneity of these tumors. The most promising direction of studies is immunotherapy. But at this stage, we cannot say that there is an effective monotherapy for glioblastoma. The combination treatment with radiation therapy and chemotherapy increases the mutational load, the expression of stress and other factors, therefore, the researchers pin great hopes on the combined methods of treatment.