Relevance. Small intestine cancer is extremely rare cancer among the Russian population with the incidence of less than 1 per 100,000 populations. in 2019, 1,643 cases of small intestine cancer were recorded in Russia, including 750 cases among the male population, and 893 among the female population. only since 2011 state statistics provides for the inclusion of primary cases of small intestine in a separate line in the state report form № 7. in 2019, none of the small intestine cancer cases was registered in four administrative territories of Russia, and only one case was registered in 13territories among the female population. in the North-Western Federal district (NWFD) of the Russian Federation, 187 primary cases of small intestine cancer were diagnosed in 2019; the standardized incidence rates were 0.91 and 0.57 0/0000 for men and women, respectively. more than 1,200 people die from small intestine cancer annually in Russia, and approximately 130 people die from this cancer in the Northwestern Federal district of the Russian Federation. the standardized mortality rates among the population of Russia and the Northwestern Federal district of the Russian Federation for men and women are 54 and 0.58 per 100,000 and 0.33 and 0.37 per 100,000, respectively. The purpose of the study was to analyze small intestine cancer incidence and mortality rates in the population of Russia. Material and methods. The population-based cancer registries of IARC, P.A. Herzen institute of oncology, N.N. Petrov Research institute of oncology as well as the population-based cancer registries of the Northwestern Federal District of the Russian Federation were used. Standard methods of oncology statistics were used. Results. the study, for the first time in Russia, made it possible to estimate the prevalence of small intestine cancer, which is much less common in Russia than in the USA and in other economically developed countries. Conclusion. In females, a significant decrease in standardized mortality rates of small intestine cancer was revealed. in males, this rate remained almost unchanged. a positive dynamics of annual mortality rates, especially within the first year of follow-up, was found.

Risk factors for renal cell cancer (RCC) recurrence, including its local form, include stage and high Fuhrman grading system score, regional lymph node involvement, microvascular invasion, tumor necrosis, positive surgical margin, and sarcomatoid or rhabdoid tumor differentiation. Objective. The study analyzes data from Moscow Research Oncological Institute named by PA Herzen to determine the predictors of local recurrence of kidney cancer based on the data from surgically treated patients with local recurrent RCC. Material and methods. We analyzed retrospectively data from 87 patients who were divided into 2 groups: 1-st, patients with detected local recurrence of kidney cancer (n=43), and 2-nd, control group (n=44). The following predictors were evaluated: tumor size, tumor histotype, tumor stage, Fuhrman grading system, surgical margin status, tumor necrosis, sarcomatoid and rhabdoid changes, microvascular invasion, hemorrhage and invasion of collecting system components (CSS), renal capsule, and perirenal cellular tissue and primary treatment. Results. The risk of local recurrence was higher in the primary tumor, over 40 mm in diameter (OR=5.8, p<0.001), as well as microvascular invasion and focal hemorrhage (OR=15.1, p=0.001 and OR=3.3, p=0.008, respectively). Both univariate and multivariate analyses showed a negative effect on the risk of local RCC recurrence only for tumor necrosis (OR=15.4, p<0.001 and OR=53.6, p=0.002, respectively) and high Fuhrman grade (OR=10.9, p=0.042 and OR=5.7, p=0.032, respectively). The most significant predictors of local renal cancer recurrence are tumor necrosis (p<0.001), microvascular invasion (p=0.019), positive surgical margin (p=0.009), and high Fuhrman grade (p=0.04). High Fuhrman grade (3–4) of malignancy (HR=1.9, p=0.042), tumor diameter (HR=1.0, p=0.054), positive surgical margin (HR=3.5, p=0.001), and tumor necrosis (HR=2.3, p=0.029) were found to be the most significant factors influencing 5-year local recurrence-free survival rate. Conclusion. The course of renal cell cancer is determined by multiple interrelated and independent prognostic factors.

Background. Pancreatic ductal carcinoma (PDC) with involvement of the superior mesenteric vein (SMV) or/ and portal vein (PV) remains a discussible subject. We have evaluated vein invasion as a criterion of borderline resectability and long-term outcome. Material and methods. In our center, 68 patients underwent either 65 standard pancreatoduodenal resections or 3 pancreatoduodenectomies for PDC. Resection of SMV/PV was performed in 18 cases (26.5 %). Three patients received neoadjuvant chemotherapy (NACT), and adjuvant chemotherapy (ACT) was assigned to 37 patients (54.4 %). Results. Morbidity (42.0 vs 50.0 %, р=0.590) and mortality rates (4.0 vs 16.7 %, р=0.111) had no significant differences in groups of standard and angioplasty operations respectively. ACT was completed in 10 (16.7 %) patients only. There was true vein invasion in 12 of 18 patients with vein resection. рN+ (р=0.012) and angioplasty by itself (р<0.001) were found out as independent predictors of overall survival (OS). the median OS was 9.4 mo in patients with vein resection. in the group of standard operations, the median OS was 26.9 mo (р<0.001). The median OS in patients with vein resection and complete chemotherapy was 17.7 mo in contrast to 8.9 mo in those who did not receive chemotherapy (р=0.439). Conclusions. PDR with vein resection and incomplete chemotherapy cannot be regarded as a reasonable procedure. PDR with vein resection may be appropriate after efficient NACT.

Development of personalized approaches to diagnosis, treatment and prognosis of colon cancer (CC) still remains challenging. Levels of circulating tumor (CTC) and cancer stem cells (CSC) are promising non-invasive prognostic factors. Our aim was to assess the overall survival (OS) of patients with stage II–IV CC with different levels of CTCs as well as to enhance their prognostic value by additionally determining the level of CD44+ CSCs. Material and methods. The study included 299 patients with stage II–IV CC. All patients underwent surgery followed by adjuvant chemotherapy (FOLFOX). patients with stage IV CC with resectable liver metastases underwent simultaneous resection of the primary tumor and liver metastases, followed by FOLFOX chemotherapy. the proportion of CTCs was evaluated before surgery using Veridex CellSearch™, and the level of CD44+ CSCs was determined in the tissue of the removed tumor by the IHC method. OS was studied in patients with different CTC levels, cumulative OS was calculated by Kaplan–Meier`s method. prognostic algorithm was designed by logistic regression analysis and cox proportional hazards model. Results. OS was found to be lower in patients with higher CTC levels divided into ranges: 0, 1–3, 4–9, ≥10 (χ²=11.59, p=0.009); thus enabling us to use it for prognosis. its prognostic value is enhanced by estimation of CD44+ CSC in tumor. Statistically significant conjugation between CTC and CD44+ ranges was found. an increase in CTC level by 1 range resulted in the increase in the risk of fatal outcome by 1.58 times (р=0.002); the additive increase in CD44+ expression ≥10 % resulted in the increase in the risk of fatal outcome by 7.2 times (p<0.001). For individual risk assessment, a model for calculating the prognostic coefficient K with high diagnostic sensitivity and specificity was developed, and its mathematical expression was proposed. the value of K≥0.411 indicates a high risk of adverse outcome. Conclusion. The prognostic algorithm for the risk of unfavorable outcome of patients with CC, based on the assessment of CTC and CD44+ CSC levels, was developed.

Breast cancer is the most common cancer in women worldwide. However, the allostatic load in breast cancer patients has not been sufficiently studied. Objective: to study the allostatic load in middle-aged and elderly patients with breast cancer. Material and methods. The study included 65 middle-aged and 60 elderly patients with histologically confirmed breast cancer and 45 people aged 60-74 years, who had no breast cancer. The allostatic load was studied in these three groups according to the level: systolic and diastolic blood pressure, total cholesterol, triglycerides, high and low density lipoproteins, glucose, albumins and waist circumference. Results. The allostatic load score was significantly higher in elderly breast cancer patients than in middle-aged breast cancer patients (4.3 ± 0.3 points versus 2.9 ± 0.2 points, p<0.01). In addition, the allostatic load score in the middle-aged patients with breast cancer was significantly higher (2.7 ± 0.2 points) than in people of the same age, who had no breast cancer (1.6 ± 0.1 points). In elderly patients, the allostatic load score was also significantly higher in patients with breast cancer than in people without breast cancer (4.3 ± 0.3 points and 2.9 ± 0.2 points, respectively; p<0.001). Significant differences in the allostatic load parameters, such as the levels of total cholesterol (5.8 ± 1.3 mmol/l versus 4.0 ± 0.8 mmol/l), and albumin (45.1 ± 7.4 % versus 61.4 ± 7.6 %) were found between breast cancer patients aged 60-74 years and people of an identical age, who had no breast cancer. statistically significant differences in allostatic load biomarkers, such as systolic blood pressure, diastolic blood pressure, blood levels of triglycerides and glucose, and waist circumference were found between elderly patients with breast cancer and age controls (without breast cancer). The content of triglycerides in the blood of patients aged 60-74 years with breast cancer was 1.8 times higher than that in patients of the same age with no breast cancer (p<0.001). The blood glucose level was significantly higher in patients with breast cancer than in the age controls (5.8 ± 1.2 g/l versus 4.4 ± 1.1 g/l, p<0.01). Conclusion. The allostatic load and its variables should be used as biomarkers of increased risk of breast cancer.

The purpose of the study was to assess the prognostic significance of a scaffolding NEDD9 protein in patients with non-small cell lung cancer (NSCLC). NEDD9 (Neural precursor cell expressed, developmentally down-regulated 9) is a scaffolding protein in many intracellular protein cascades, such as PI3K-AKT-mTOR, Ras-ERK, which play key roles in tumor progression. several studies define the regulatory role of NEDD9 in progression of several solid cancers, including non-small cell lung cancer (NSCLC), however its role as a prediction biomarker is minimally assessed. Materials and methods. In the current study quantitative immunohistochemical (IHC) approach was utilized to characterize NEDD9 expression in a cohort of NSCLC primary tumor samples (n=16), and correlative statistical analysis was performed between NEDD9 expression and a set of patients’ clinical and pathological characteristics. Results of the IHC analysis were validated using broader TCGA RNAseq dataset (n=566). Results. The study demonstrated significant difference between the expression of Nedd9 in stage iii tumors versus stages II and IV (p<0.05). Next, NEDD9 expression level was approximated to high and low (based on median h-score=56.14) and statistical survival analysis revealed a positive correlative trend between the decreased expression of NEDD9 and the decrease in the overall (OS) and progression-free survival (PFS) of the patients. Analysis of TCGA dataset harboring RNA seq data confirmed statistically significant correlation (p=0.05) between low NEDD9 expression and decreased OS. Conclusion. This study suggests that the expression of the scaffolding protein NEDD9, both at the protein and RNA levels, positively correlates with a negative prognosis in NSCLC, suggesting that it can potentially be used as a novel biomarker of disease progression. Further basic and clinical research defining the role of NEDD9 in the progression and metastasis of NSCLC are strongly warranted.

The treatment of colon cancer with a mesenchymal-like phenotype poses a great challenge. Purpose of the study: to research expression of FRMD6, ZEB1, HTR2B, CDX2 in the primary tumor tissue with relation of the clinical and pathological features of colon cancer. Material and methods. a combined analysis of the expression of FRMD6, ZEB1, HTR2B, CDX2 with pathological criteria was performed in 100 patients with T1–4bN0–2bM0  colon  cancer.  Results  of  the  study  show  that  tumors  with  mesenchymal  signs  are characterized by a large size of the primary tumor, a high grade of differentiation, regional metastases, and eventually advanced stage of the disease. The frequency and expression levels of FRMD6, ZEB1 and HTR2B are depended of grade of adenocarcinoma. in cases with positive expression and a high percentage of expression of these proteins in the cancer cells, the degree of tumor morphological anaplasia increases. Conclusion. The study made it possible to reveal the relationship of IHC markers (FRMD6, ZEB1, HTR2B, CDX2) with tumor characteristics that determine the outcome. The studied markers may have prognostic and predictive value in treatment approaches of colon cancer.

Purpose: To study the relationship between the -31G/C (rs9904341) polymorphism in the promoter region of the survivin protein gene and the predisposition to bladder cancer (BC) in patients of the Krasnoyarsk region. Material and methods. The allelic composition of the studied gene was determined in a group of 158 BC patients, consisting of 30 women and 128 men (mean age 65.6 ± 10.7, median: 66.5; C₂₅–C₇₅: 59–72). The control group included 117 healthy donors and consisted of 27 women and 90 men with an average age of 60.2 ± 5.1 (median: 60; C₂₅–C₇₅: 57–63.25). The allelic composition was determined using the bioluminescent method. A sample with the GC genotype confirmed by sanger sequencing (center for collective use “genomika”, Novosibirsk, Russia) was used as a control. The Mann–Whitney U test was used to compare quantitative data. the studied sample was in Hardy–Weinberg equilibrium (p>0.5). The pearson χ² test was used to compare the frequencies of gene variants among BC cases and control samples. The association between variants rs9904341 and BC was assessed in terms of odds ratio (OR) with a 95 % confidence interval (CI); p values<0.05 were considered significant. Results. The allelic composition was determined for the genes of patients and control group participants: GG – 62 (39.2%) vs 43 (36.8%); GC – 82 (51.9%) vs 54 (46.2%); CC – 14 (8.9%) vs 20 (17.15%). The relationship between the presence of the C allele and BC was assessed using the recessive inheritance model, combining all carriers – heterozygotes and homozygotes. The frequency of occurrence of genotypes for patients and the control group was established: GG + GC – 144 (91.1%) vs 97 (82.9%); CC – 14 (8.9%) vs 20 (17.1%). Thus, carriers of the CС genotype were significantly less in patients: OR (95% CI) 0.47 (0.23–0.98), p=0.04. The relationship with tumor invasion was not significant (p=0.08). Conclusion. Based on the results of detecting the rs9904341 (G/C) polymorphism among BC patients of the Krasnoyarsk region, a protective effect of the carriage of the CC genotype was found. In order to study the allelic composition with the threat of recurrence of the disease, additional research is needed.

Background. Breast cancer (BC) is the most common female malignancy worldwide. Partner And Localizer of BRCA2 gene (PALB2) is directly involved in DNA damage response. Germline mutation in PALB2 has been identified in breast cancer and familial pancreatic cancer cases, accounting for approximately 1–2% and 3–4%, respectively. The goal of this report was to describe new PALB2 mutation in a young Yakut breast cancer patient with family history of cancer. Material and Methods. Genomic DNA were isolated from blood samples and used to prepare libraries using a capture-based target enrichment kit, Hereditary Cancer Solution™ (SOP HiA GE NETICS , Switzerland), covering 27 genes (ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53 and XRCC2). Paired-end sequencing (2 × 150 bp) was conducted using NextSeq 500 system (Illumina, USA ). Results. Here we describe a case of a never-before-reported mutation in the PALB2 gene that led to the early onset breast cancer. We report the case of a 39-year-old breast cancer Yakut woman with a family history of pancreatic cancer. Bioinformatics analysis of the NGS data revealed the presence of the new PALB2 gene germinal frameshift deletion (NM_024675:exon1:c.47delA:p.K16fs). In accordance with dbPubMed ClinVar, new mutation is located in codon of the PALB2 gene, where the likely pathogenic donor splice site mutation (NM_024675.3:c.48+1delG) associated with hereditary cancer-predisposing syndrome has been earlier described. Conclusion. We found a new never-before-reported mutation in PALB2 gene, which probably associated with early onset breast cancer in Yakut indigenous women with a family history of pancreatic cancer.

Introduction. Currently, most of the drugs used in tumor therapy are highly toxic and cause various toxic effects. Therefore, many drug delivery methods are being developed. The use of nanotechnology is one of the most promising methods. The use of magnetic iron oxide nanoparticles as antitumor agents makes it possible to prevent off-target cytotoxicity and other side effects of traditional chemotherapy. The use of nanoparticles is limited by their low efficiency. the Fe₃O₄/Fe galvanic couple makes it possible to control the release of toxic iron ions and, accordingly, the activity of nanoparticles. Purpose. The aim of this study is to develop new Fe₃O₄-Fe nanoparticles with a core-shell structure with antitumor activity in vitro. Nanoparticles containing from 5 % to 90 % iron were synthesized, and a systematic study of the structural, textural, charge, morphological, and magnetic properties of nanoparticles, as well as their in vitro activity against the MCF-7 and HeLa tumor lines, was carried out. Methods. Fe₃O₄-Fe nanoparticles were obtained by electric explosion of an iron wire in a mixture of gases: argon and oxygen. The mass fraction of the components was regulated by varying the ratio of the components of the gas mixture. The physicochemical properties of nanoparticles were studied using X-ray phase analysis, thermal desorption of nitrogen, transmission electron microscopy, and microelectrophoresis. Antitumor activity was studied using the MTT test against HeLa and MCF-7 cell lines. Results. As a result of the electric explosion of an iron wire in an argon + oxygen gas mixture containing oxygen in the range of 1 – 5 vol. %, Fe₃O₄-Fe NPs with 5 – 90 % wt. Fe₃O₄, respectively. The study of the physicochemical properties of nanoparticles showed that the zeta potential does not depend on the content of Fe₃O₄ in NPs and is -30 mV. The change in the specific surface area and the average particle size passes through a maximum at the content of Fe₃O₄ W=20 %, which can be explained by the mechanism of oxide phase formation during an electric explosion. Using the MTT test, it was found that nanoparticles containing 5 wt. Fe₃O₄, in the presence of which, at a concentration of 1 mg/ml, the number of living cells decreased to 16 % relative to the control. Conclusion. In this work, we have shown for the first time that Fe₃O₄-Fe NPS in the concentration range of 50–100 µg/mL can be used as an antitumor agent. The ability to control the magnetic properties of NPs can be used to target a specific area of tumor tissue using an external magnetic field, and the established relationship between the magnetic moment and the activity of NPs in relation to the MCF-7 cell line has great prospects for clinical application.

The aim of the study was to assess the response to preoperative radiotherapy (RT) in patients with G2-G3 rectal neuroendocrine tumors (NETs). Material and methods. Case reports involving patients who were given treatment at the N.N. Blokhin National Medical Research Center of Oncology from 2000 to 2020 were retrospectively studied. Patients with histologically verified neuroendocrine tumors of the rectum and anal canal (G2 and G3, Ki67>3%), who underwent preoperative radiotherapy (RT) or chemoradiotherapy (CRT) were included into the study. the study excluded patients who received palliative RT/CRT, patients with primary multiple synchronous or metachronous tumors, and patients with unresectable liver metastases. Staging was performed on the basis of MRI of the pelvis, CT scan of the chest and abdomen with intravenous contrast. The main assessment parameter was the response rate to treatment according to the RECIST criteria, and additional parameters were the frequency of pathological response according to DWORAK classification and overall and relapse-free survivals. Statistical analysis was conducted using the IBM SPSS software package (version 25). Results. The median follow-up time was 24 months. the follow-up time of a patient with G3 neuroendocrine cancer was 64 months without the evidence of disease progression. The 5-year OS and DFS for patients with G2-G3 rectal NETs were 64.3 % and 53.3 %, respectively. Conclusion. Long-term progression-free survival in 2 out of 3 patients with G3 neuroendocrine cancer (1 of them with a complete clinical response) and in 3 out of 4 patients with G2 neuroendocrine tumors was obtained.

Purpose of the study: Analysis of available data on geno-phenotypic correlations and atypical forms of neurofibromatosis type 1. Material and methods. We searched for relevant sources in the Scopus, Web of Science, PubMed systems, including publications from May 1993 to October 2021. Of the 318 studies  we identified, 59 were used to write a systematic review. Results. We found studies describing atypical forms of neurofibromatosis type 1 with an erased course without manifestation of a tumor syndrome, which are caused by specific mutations in the NF1 gene (causing substitutions of amino acids in neurofibromin: p.Arg1038, p.Met1149, p.Arg1809, or deletion of amino acids: p.Met990del, p.Met992del). NF1 patients with microdeletions are characterized by more severe disease symptoms (more often facial dysmorphism, skeletal and cardiovascular abnormalities, learning difficulties, and symptomatic spinal neurofibromas). mutations of splicing sites and extended deletions of the NF1 gene are associated with early manifestation of tumors, mutations at the 5’-end of the gene, causing a shortening of the protein product, are associated with optic nerve gliomas. the mutation c.3721C>T (p.R1241*) correlated with structural brain damage, and c.6855C>A (p.Y2285*)  with  endocrine  disorders. the  manifestations  of  NF1,  similar  to  lipomatosis  and Jaffe-Campanacci syndrome, not associated with a specific type of mutation are described. Conclusion.  In spite of pronounced clinical variability of the disease, even among members of the same family, several studies have described genotype-phenotype correlations. Therefore, the role of modifier genes and epigenetic factors in the pathogenesis of NF1 is assumed, since the neurofibromin protein has a complex structure with several functional domains. It has been shown that the severity of the tumor syndrome is influenced by the methylation characteristics of NF1 gene and adjacent areas. in addition, NF1 gene is associated with a variety of microRNAs. therefore, targeted therapy aimed at specific non-coding RNAs to restore normal expression of NF1 gene can become a promising treatment for NF1.

Introduction. Meningiomas are the second most common central nervous system (CNS) tumors in adults. most meningiomas are benign tumors. Anaplastic and atypical meningiomas account for 25% and have a high recurrence rate even after radical tumor resection and radiotherapy. The prognosis of patients with anaplastic meningiomas remains disappointing; most of them die within the first 2 to 5 years after surgery. Purpose: to discuss the challenges in diagnosis and treatment of recurrent meningiomas, to identify the causes of tumor progression, and to assess the clinical features and radiographic findings as well as specific pathomorphological and molecular genetic characteristics. material and methods. We searched for publications in the Pubmed, EMBASE, Cohrane Library and eLibrary databases published between January 2000 and January 2019 on the issue of recurrent intracranial meningiomas, in particular atypical and anaplastic meningiomas. Results. The review systematizes data on the prognostic factors for survival, relapse-free period, and disease progression. particular attention was paid to the radical resection of the tumor and the assessment of the grade of anaplasia. The current data on radiotherapy and drug therapy were presented.  the controversial issues of approaches to the assessment of morphological prognostic criteria were discussed. The current knowledge on the most common genetic mutations in meningiomas, the prospects for their study and use for targeted therapy were presented. Conclusion. The management of meningioma still presents some unresolved issues.  There are no optimal standards for diagnosis and treatment of patients with meningiomas that would take into account biological characteristics, including growth characteristics and molecular genetic profile. There are no clear prognostic criteria for recurrence and continuity in further management after surgical treatment, which affects the mortality rate and quality of life in this category of patients. New fundamental data that will determine a different strategy in the treatment of intracranial meningiomas are needed.

Macrophages  are  key  components  of  the  innate  immune  system. The  variability  of  the  macrophage’s participation in tumor progression, determined by their functional polarization, opens up a wide prospect for modulating their functional profile, primarily in the direction of increasing antitumor activity. The purpose of the study was to provide up-to-date data on the process of macrophage polarization, mechanisms of its regulation, polarization markers and induction factors. Material and methods. A search was made for available literature sources published in Web of Science, Scopus and other databases. more than 160 sources devoted to the study of the process of macrophage polarization were found, of which 121 were included in this review. Results. This review presents data on the molecular mechanisms and gene signatures associated with M1 and M2 polarization of macrophages. We displayed information on metabolic, phenotypic characteristics and cytokine profile of M1- and M2-macrophages, as well as highlighted data on polarization factors and targets of their action. Conclusion. The information presented in the review can serve as an information base for the development of experimental and clinical approaches for editing the functional profile of macrophages in order to control their involvement in various pathological processes.

Endometrial cancer is the most common cancer of the female reproductive organs. The purpose of the study was to summarize the available data on the role of angiogenic markers in the development, progression and prognosis of endometrial cancer. Material and methods. A literature search was conducted using Medline and Pubmed databases using the key words: “endometrial cancer”, “endometrial hyperplasia” and others. 56 publications were selected to write this review. Results. Currently, there is a variety of different data on the relationship between molecular markers of angiogenesis in endometrial cancer and the prognosis of endometrial cancer. The article summarizes the results of the most recent studies devoted to the study of angiogenic markers of endometrial cancer, as well as the characteristics of the microvasculature. We focused on the prognostic and diagnostic values of these morphological and molecular changes. particular attention was  paid  to  the  inactivation  of  the  oncosuppressive  protein  PTEN,  an  inhibitor  of  the  PI3K/Akt/mTOR-signaling pathway, which plays an important role in the pathogenesis and prognosis of endometrial cancer. Conclusion. Many of the markers of angiogenesis can be used to assess the development and prognosis of endometrial cancer. However, conflicting research results with respect to some markers require further study, their validation, and subsequent implementation into practice.

The purpose of the study. Multiple primary malignant neoplasms or polyneoplasia are a phenomenon of tumorigenesis and one of the little-studied categories in modern clinical oncology. The increase in the cancer incidence, as well as the need to make difficult decisions about further treatment strategy, enhance the relevance of studying multiple primary malignant neoplasms. This review discusses the current positions of medicine in relation to this category of malignant neoplasms, and presents a case report of a patient with this disaese. Material and methods. We have analyzed the results of international studies on the management of patients with multiple primary cancer. the search for relevant sources was carried out in the Web of Science, Scopus, Medline systems with a chronological interval of 2016–2021. of the analyzed studies, 60 were used to compile a systematic review with a case report. Results. The analysis showed that timely diagnosis and improvement of cancer screening programs are necessary to improve the control of these tumors. Psychological work with a patient, strengthening of his commitment to therapy and the implementation of medical recommendations are integral parts of improving cancer care for patients with such disease. Conclusion. A comprehensive analysis of multiple primary malignant tumors requires long-term follow-up of a large population, taking into account genetic factors, environmental factors, exposure to smoking and nutrition, and comorbid pathology. Timely diagnosis and improvement of cancer screening programs are necessary to improve the control of multiple primary malignant tumors.

Backgraound. High-grade serous ovarian carcinoma (HGSOC) is the most common type of ovarian cancer. The prevalence of BRCA1/2 germline mutations is the highest in HGSOC. patients with germline BRCA gene mutations are more likely to respond to platinum-based chemotherapy. Clinical trials demonstrate the effectiveness of PARP inhibitors in the treatment of BRCA-associated ovarian cancer. Re-administration of PARP inhibitors after response to platinum-based chemotherapy demonstrates an increase in progression-free survival rates regardless of BRCA status. it is important for understanding the development of molecular mechanisms of resistance to platinum drugs and PARP inhibitors, as well as for developing new treatment strategies  and  tools  to  overcome  resistance. Case  description. This  clinical  case  of  BRCA-associated hereditary ovarian cancer demonstrates the efficacy and good tolerability of PARP inhibitor maintenance therapy following the treatment of the first relapse, as well as the efficacy of re-administration of PARP inhibitors following the treatment of the second relapse. The short-course of re-treatment with PARP inhibitors was accompanied by the development of multidrug resistance. the overall survival time was 112 months. Conclusion. The presence of mutations in BRCA1/2 genes is a promising justification for the administration of maintenance therapy with PARP inhibitors. Re-administration of PARP inhibitor maintenance therapy for relapsed ovarian cancer is currently being considered as a possible therapeutic option. deciphering the molecular mechanisms of resistance to PARP inhibitors is of paramount importance for the development of new treatment strategies and tools to overcome chemoresistance, re-sensitization of the tumor to platinum-based drugs or PARP inhibitors.

Background. SCC of the gallbladder is characterized by more rapid and invasive growth with infiltration of the adjacent organs and less spread to the lymph nodes compared to adenocarcinoma of the gallbladder. It is a rare neoplasm that accounts for 1.4–12.7 % of gallbladder tumors. SCC of the gallbladder has a poor prognosis. symptoms usually appear later when the disease has progressed and the malignancy has reached advanced stages. therefore, usually, the patients expire soon following the diagnosis. the etiology of the SCC of the gallbladder is complex and is mostly associated with gallstones. Case description. We report a case of a 56-year-old man that had been suffering from colicky abdominal pain in the right upper quadrant for about two weeks before his admission. He did not have nausea, vomiting, shortness of breath, fever, lack of appetite, or weight loss. after evaluation, a diagnosis of acute cholecystitis was established and antibiotic therapy was initiated. However, he did not respond to medical therapy and underwent surgery. A tumor mass was detected during surgery. therefore, cholecystectomy and extended right hepatectomy were performed. The pathological evaluation of the biopsy specimen revealed squamous cell carcinoma. consequently, he underwent radiotherapy and chemotherapy and was followed up for two years. He acquired complete tumor remission. Conclusion. The present case highlights the requirement of considering further investigation on the histogenesis of SCC of the gallbladder.