Aim. Summarizing current insights into the pathogenesis of breast cancer (BC) from the perspective of candidate gene involvement, specifically matrix metalloproteinase genes (MMPs), and their clinicopathological significance.

Materials and methods. Source retrieval for the study was conducted using PubMed, Medline, Cochrane Library, eLibrary, NHGRI-EBI Catalog of GwAS databases. Publications from January 2004 to December 2022 were included. A total of 158 sources related to the role of MMPs in BC development were identified. Search queries encompassed associations of different MMPs loci with BC formation and progression. This review included 60 selected works, adhering to inclusion criteria based on comprehensive genome-wide association studies (GwAS) and representative patient cohort association studies with adequate statistical power. Data encompassing clinicopathological significance (association with BC molecular subtype, survival, disease prognosis, metastasis risk, and malignancy grade) of MMPs polymorphic markers were incorporated. Excluded were data from MMPs gene association studies with non-carcinoma breast diseases and studies conducted on small, non-representative patient and control samples.

Results. The clinical presentation of BC, treatment nuances, and patient survival depend on the interaction of various risk factors, including genetic ones. The association between MMPs gene polymorphisms and BC is actively investigated. Well-studied polymorphisms include MMP1 (rs1799750), MMP2 (rs243865), and MMP9 (rs3918242, rs17576, rs2250889, rs3787268), which have shown correlations with BC development, metastasis, and survival. Literature data significantly support the association with BC – risk susceptibility, malignancy grade, regional and distant metastasis, and patient survival – for polymorphic variants 2G rs1799750 MMP1, T rs3918242 MMP9, G rs17576 MMP9,  G rs2250889 MMP9 (risk factors), and T rs243865 MMP2 (protective factor). In contrast, data on most other MMP polymorphisms (rs3787268 MMP9, rs1940475 MMP8, etc.) are limited and often discordant.

Conclusion. Continuing research into the association between MMPs gene polymorphisms and BC is an important scientific and practical task, aiming to expand empirical knowledge in this domain and ultimately establish definitive insights into their influence on disease progression and prognosis.

Background. The risks of recurrence and death in patients with colorectal cancer (CRC) can vary significantly, even among patients with similar clinicopathological features, due to the high level of tumor heterogeneity. Existing molecular classifications have relatively limited value. Gene signatures identified through whole-exome / whole-transcriptome analyses may play a more significant role.

Aim. To systematize literature data on expression signatures and describe their prognostic and predictive value in the context of non-metastatic CRC.

Results. This review describes contemporary aspects of personalized approaches in the treatment of CRC applied in clinical practice: mutational and microsatellite status, the significance of the primary tumor’s location. Data on multi-gene signatures and tumor expression characteristics are also presented. Several signatures allow predicting the risk of recurrence, disease-free, and overall survival in resectable and locally advanced CRC. Additionally, the correlation between drug sensitivity and DNA repair gene signatures is demonstrated. Data on the correlation of expression signatures with proteins, phosphoproteins, and their role as prognostic and predictive factors in non-metastatic CRC are provided.

Conclusion. The practical application of gene signatures currently lacks significance. Due to the scattered nature of data and the wide variety of examined signatures, making meaningful conclusions about their practical value is impossible. However, it is possible that in the future, the use of gene signatures will lead to a more accurate prognosis, new approaches to drug therapy, and improved outcomes for patients with CRC.

Chemotherapy for cancer is associated with a significant risk of severe side effects due to the effects of cytostatics on healthy cells. Targeted oncotherapy is an innovative approach to cancer treatment that targets specific protein structures and metabolic pathways that are highly likely to be inherent in tumor cells. Historically, immunoconjugates (IC) were among the first targeted therapy agents, along with monoclonal antibodies, to be approbated and subsequently approved for clinical use. Traditionally, an IC is described as a monoclonal antibody covalently linked to a therapeutic component via a linker. Due to their vector component, these drugs allow the application of selective effects on epitope-defined targets, which significantly increases the therapeutic index of highly toxic antitumor agents. In addition, targeting therapy helps to overcome drug resistance of tumors and improve the prognosis of the disease. Herewith, the pharmaceutical design of IC requires comprehensive consideration of specific aspects such as physicochemical properties of the conjugated substance, optimal choice of immunoglobulin class G isotype, biochemical properties of the linker and conjugation methods. A comprehensive study of these aspects will not only optimize the design of IC, but will also contribute to the widespread use in clinical practice and expand the range of applications of such drugs. This review presents the evolution of the antibody – drug conjugate concept in the context of the application of these drugs in oncotherapy. The aspects of structure and specific features of strategies of drug-drug conjugation with monoclonal antibody, which are basic for IC design, are also discussed and summarized.

Background. Extracellular vesicles (EVs) play a major role in the progression of skin melanoma: contributing to immune evasion, acquisition of resistance to drug therapy and metastasis. By affecting the assembly process of EVs as well as the secreted vesicles of tumor cells and their microenvironment, a significant reduction in the number of vesicles capable of transmitting signals and transporting macromolecules can be achieved. Thus, blocking this information transmission system at its different levels may be a new way of drug therapy of malignant neoplasms. Currently, there are a number of small synthetic molecules that disrupt the synthesis of exosomes and microvesicles (inhibitors of neutral sphingomyelinase, calpain, Rho-associated protein kinases) and their conjugates to combat exosomal mechanisms of resistance to immune checkpoint inhibitor therapy. In addition to inhibition of EVs assembly, membrane proteins of EVs (heat shock protein family HSPA / HSP70, laminin-binding integrins α3β1 and α6β) are considered as targets of targeted therapy. Some receptors providing specific fusion of vesicles with recipient cells have also been identified (CD46 receptor involved in the internalization of exosomes of a tumor cell line with brain metastases, SK-Mel-28, many adhesive molecules belonging to the family of integrins, immunoglobulins and selectins, as well as CD44 and tetraspanins.

Aim. To review the available attempts to influence the biogenesis of tumor EVs (EVs) in order to develop a possible therapeutic strategy for the treatment of skin melanoma that has escaped the control of immune and targeting drugs.

Materials and methods. In this work we present the results of research on melanoma of skin EVs and ways to influence EVs communication. The relevant sources were searched in web of Science, PubMed, eLibrary.ru. The Elicit tool for searching scientific articles was also used.

Conclusion. In this work we analyzed the effect of small synthetic molecules, monoclonal antibodies and regulatory RNAs on different parts of tumor EVs biogenesis: assembly, secretion of EVs, and their transport. Conclusions are drawn about the validity of anti-EVs therapy to date and the possibility of its application in the aspect of skin melanoma.

Background. The tumor microenvironment can both restrain tumor growth and promote disease progression. Therefore, the study of tumor-infiltrating lymphocytes (TILs) subpopulation composition is an urgent and significant topic.

Aim. To characterize the immune microenvironment of renal cancer by flow cytometry.

Materials and methods. The study included blood, kidney tumor and normal tissue of the removed kidney of 32 patients with clear cell renal cancer treated at N. N. Blokhin National Medical Research Center of Oncology. Kidney tissue was obtained during surgical removal of the tumor (resection / nephrectomy). A fragment of tumor and normal tissue was taken for analysis under the control of a morphologist. Blood for the study was taken on the day of surgery. Immunologic study was performed by flow cytometry. Kidney tissue was preliminarily homogenized and cell suspension was stained, as well as peripheral blood, with monoclonal antibodies to CD45, CD3, CD4, CD8, CD16⁺CD56⁺, CD19, CD28, CD279, CD11b labeled with different fluorochromes.

Results. T-lymphocytes and natural killer (NK) cells have a pronounced inverse correlation, which allowed us to distinguish two (n = 32; 18 / 14) variants of tumor immune microenvironment. T-cell variant, with predominance of CD3⁺CD8⁺ cells over CD3⁺CD4⁺ lymphocytes, and NK cell variant – increase in the number of NK cells with a pronounced decrease in the proportion of T-lymphocytes at the expense of CD3⁺CD8⁺ lymphocytes. The two variants are based on the difference of effector link – predominance of cells of innate (NK) or adoptive (CD3⁺CD8⁺) immunity. TILs immune profiles also differed in the number of CD8⁺PD1⁺ cells – in the T-cell variant their number was 2 times higher than in the NK cell variant. The similar distribution concerned CD4⁺ Treg cells.

Conclusion. Two immunologically competitive variants of renal tumor microenvironment were revealed – T-cell variant, characterized by a greater degree of infiltration and concentration of T-regulatory cells; NK cell variant, with an insignificant degree of infiltration and a pronounced strengthening of the effector link in the tissue and proinflammatory activity of peripheral blood.

Background. The oncological incidence in the world and the Russian Federation of rectal cancer (RC), prostate cancer (PC) and cervical cancer (CC) over the past 10–15 years remains high, with overall incidence of the pelvic organs cancer up to 25 % of the total. Radiation therapy is included in the complex of therapeutic measures in 50–70 % of cancer patients. The main feature of radiation therapy of patients with malignant neoplasms is the effect on both tumor and healthy cells of surrounding tissues. The development of radiation damage to healthy tissues, expressed in radiation reactions (RR) and complications lead to a deterioration in the quality of life. Unfortunately, it is currently not possible to predict which of the patients will develop radiation injuries above grade 1 and at what time.

Aim. To assess the risks of RR in patients with diagnoses of RC, prostate cancer and cervical cancer who underwent radiation therapy.

Materials and methods. The study included 759 patients, including 387 CC, 175 PC, and 197 RC, who received radiation therapy from 2011 to 2019 in the medical institutions of St. Petersburg and the Leningrad region.

Results. More than 30 factors that characterized patients, tumor features and concomitant therapy options were studied. Twelve of them turned out to be significant. In order to establish the main determinants (factors) associated with the risk of radiation reactions, a discriminant analysis was carried out. A formula has been created to calculate the probability of developing RR. We conducted an additional study on changing the timing of the introduction of hydrogel compositions, in which a decrease in the frequency of radiation-induced cystitis was noted.

Conclusion. Discriminant analysis revealed predictors of RR in patients with RC, CC, and PC out of 30 factors studied. From the results of discriminant analysis, formulas for predicting the probability of developing acute RR in patients with diagnoses of RC, CC, and PC who received radiation therapy were derived. The change in the time of administration of hydrogel compositions before, during and after the end of radiation therapy contributed to a decrease in the occurrence of radiation-induced cystitis compared with the control (р <0.05).

Background. Adjuvant is necessary for enhancing the efficacy of cancer peptide vaccines. Our previous work has demonstrated the efficacy of TRL-3 agonists, which include Poly(I:C) and Ridostin Pro, as part of peptide neoantigen vaccines against murine melanoma B16-F10.

Aim. To evaluate the antitumor efficacy of Ridostin Pro or Poly(I:C) against murine lymphoma E.G7-OVA.

Materials and methods. The study was performed on C57Bl / 6 mice with subcutaneously transplanted E.G7-OVA lymphoma containing the complete chicken ovalbumin sequence. The antitumor effects of Ridostin Pro and Poly(I:C) were evaluated in monotherapy as well as in vaccines containing chicken ovalbumin in addition to the adjuvant. The antitumor effect of Ridostin Pro and Poly(I:C) was evaluated when used in different vaccination regimens: in one case treatment was started after tumour transplantation and in the other case before tumour transplantation. The criteria of antitumor response were inhibition of tumour growth, increased survival of mice and cure.

Results. Ridostin Pro and Poly(I:C) both as part of the vaccine and when administered without ovalbumin increased the percentage of tumour growth inhibition and survival of mice with E.G7-OVA lymphoma. In a regime where  vaccination with ovalbumin and Ridostin Pro or Poly(I:C) was started before tumour transfection, a complete cure of the mice was shown.

Conclusion. Ridostin Pro and Poly(I:C) enhance the antitumor effect of a peptide vaccine against E.G7-OVA lymphoma.

Background. Allergies are a global medical and social problem. According to international statistics, the number of allergic diseases has increased dramatically in recent decades. In recent years, the largest increase in the incidence of bronchial asthma, pollinosis and dermatoses has been noted. Currently, significant success has been achieved in understanding the causes and mechanisms of allergic inflammation and in forming approaches to the treatment of allergic diseases. Among second-generation antihistamines, loratadine, an effective antiallergic drug, is excreted. However, in the pharmaceutical market, the range of its dosage forms is small – the drug is available in the form of tablets, capsules and syrup. Prednisolone is a drug that quickly copes with an allergic reaction and helps prevent unwanted complications. In this regard, it is proposed to develop a tablet dosage form of a combined composition. Combined technology was used in the development of model compacted tablet formulations. The release and assay of active ingredients from model tablets of different compositions were determined using the Dissolution test and by high performance liquid chromatography, respectively.

Aim. Development of loratadine and prednisolone tablets of the combined structure.

Materials and methods. Combined technology was used in the development of model compacted tablet formulations. The release of the active ingredients from the tablets was confirmed by the Dissolution test in HCl dissolution medium (0.1 M). The assay of the active ingredients in the formulation was determined by high performance liquid chromatography.

Results. The conducted studies made it possible to determine the composition of the combined tablets, which ensures the initial release of prednisolone and the subsequent release of loratadine. In the Dissolution test, the chosen model composition of tablets No. 1 provided release of 84.4 % prednisolone and 81.5 % loratadine, respectively, at the 10th and 30th minutes.

Conclusion. The possibility of preparing a tablet dosage form providing a sequence of release of active substances has been demonstrated.