The aim is to present expert-agreed guidelines for the primary prevention of cardiovasculotoxicity of anticancer therapy as part of the Cardioprotection 2025 Consensus of the Russian Society of Cardiology, the Society of Heart Failure Specialists, the Russian Association of Oncologists, and the Eurasian Association of Cardio-Oncologists. The second part of the Consensus focuses on strategies for protecting the myocardium and blood vessels before or at early stages of anticancer treatment. The document addresses the key principles of primary prevention of cardiovasculotoxicity: interdisciplinary collaboration between cardiologists and oncologists at the stage of treatment scheduling, the possibility of managing modifiable risk factors, pharmacological cardioprotection, approaches to preventive screening (including clinical evaluation, biomarkers, and imaging), non-pharmacological prevention (physical activity, nutritional status correction, artificial intelligence, and digital monitoring management), and specific features of prophylaxis in the treatment with key anticancer drug classes (anthracyclines, HER2-targeted agents, tyrosine kinase inhibitors, anti-VEGF agents, immune checkpoint inhibitors). This document aims to optimize patient management to reduce the risk of cardiovascular complications during anticancer therapy.

The DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) removes various adducts from the 3'-end of DNA, including those induced by anticancer chemotherapeutics and is therefore considered an important therapeutic target. Previously, we investigated TDP1 inhibitors as sensitizers for the anticancer drug topotecan. Now, we have demonstrated that usnic acid derivatives containing a thiazole ring with an amide linker exhibited inhibitory activity against TDP1 at micromolar and submicromolar concentrations. Moreover, the lead compound OL11-119, (R)-N-(4-(8-acetyl-1,3,7-trihydroxy-2,9a-dimethyl-9-oxo-9,9a- dihydrodibenzo[b,d]furan-4-yl)thiazol-2-yl)-4-bromobenzamide, was found to enhance topotecan-induced tumor cell death at a nontoxic concentration. Molecular docking of OL11-119 and its analog with hydrazone linker, OL9-119, a previously identified potent TDP1 inhibitor, was performed. The binding energy of OL9- 119 to the enzyme active site was shown to be lower than that of OL11-119, which correlated with the higher inhibitory activity of OL9-119 against TDP1.

In 1976, the antifungal hydroxamic antibiotic trichostatin A (TSA) was isolated from the metabolites of the bacterium Streptomyces hygroscopicus. It took 14 years to find that TSA has an effect on the proliferation and differentiation of mammalian cells by inhibiting histone deacetylase (HDAC) activity. By 2015, a single database containing the structures of about 1050 synthetic and 400 natural HDAC inhibitors had been created. Currently, five inhibitors are approved for use as anticancer agents, with dozens more compounds undergoing clinical trials. However, the implementation of new agents is severely hampered by their multidirectional action and the severity of side effects. New strategies are needed to overcome these problems, including the development of inhibitors targeting a specific class of HDACs. In addition to the most important characteristics of histone deacetylases and their natural inhibitors, this review considers current approaches to the design of selective HDAC inhibitors and the methods used to test them.

The purpose of this document is to provide updated, evidence-based recommendations for the prevention of cardiovascular toxicity associated with anticancer therapy (anthracyclines, HER2-targeted therapy, tyrosine kinase inhibitors, anti-VEGF agents, fluoropyrimidines, and immune checkpoint inhibitors). The consensus covers risk stratification, screening and monitoring (biomarkers and imaging), pharmacological and non-pharmacological cardioprotection, and patient management algorithms for the detection of subclinical and clinically significant damage to the cardiovascular system. The recommendations are structured by recommendation classes (I, IIa, IIb, III) and levels of evidence (A, B, C), and are adapted for Russian and Eurasian clinical practice.

Aim        To develop and validate a simple and clinically convenient multiparametric model combining clinical, instrumental and laboratory predictors to prognose the risk of developing cardiovascular toxicity (CVT) in patients receiving antitumor therapy with subsequent personalized stratification of prevention and treatment.Material and methods          This multicenter prospective study included 252 patients (mean age 64.8±10.4 years; 64.5% women) with large tumors and lymphoproliferative diseases who received various antitumor treatments. Demographic data, risk factors, echocardiography results, left ventricular ejection fraction, left ventricular global longitudinal strain (GLS), laboratory data (high-sensitivity troponin I/T, terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein, lipid profile) were collected. The endpoint of the study was the development of CVT within 12 months according to the criteria of the European Society of Cardiology (2022).Results    Following multivariate analysis using the Cox model, the most sensitive independent predictors of cardiotoxicity were selected: age >60 years, GLS <-18%, troponin elevation >99th percentile, and NT-proBNP concentration >300 pg/ml. A prognostic model was developed based on the identified parameters. Model validation demonstrated its high validity.Conclusion            Integration of multicomponent data into a single compact prognostic model ensures high accuracy of assessing the risk for the development of CVT and can become a simple tool for personalized monitoring and prevention in cancer patients.

Aim    Search for subclinical manifestations of cardiotoxicity in cancer patients at high and very high risk of cardiotoxicity and evaluation of the effectiveness of drug primary prevention during the antitumor treatment. Material and methods    The study included 150 cancer patients with a high and very high Mayo Clinic (USA) Cardiotoxicity Risk Score. The main group consisted of 84 patients at high and very high risk of cardiotoxicity who were prescribed cardioprotective therapy, including a fixed combination of the angiotensin-converting enzyme inhibitor (ACEI) perindopril and the beta-blocker bisoprolol with trimetazidine. The comparison group consisted of 66 patients who refused cardioprotective drugs or had intolerance to them. All patients underwent 24-hour ambulatory blood pressure monitoring (ABPM) and multibiomarker analysis, including measurements of troponin I (TnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), myeloperoxidase (MPO), soluble tumor suppressor type 2 (sST2), and two-dimensional echocardiography (EchoCG) with assessment of left ventricular global longitudinal systolic strain (LV GLS) before chemotherapy and 1, 3, 6, 9, and 12 months after the start of cardiotoxic antitumor therapy. Results    In patients of the comparison group already at 6 months, the left atrial volume index (LAVI) was significantly increased, and the left ventricular end-diastolic volume index (LVEDVi) showed a tendency towards an increase reaching a significant difference by 9 months of observation. In the main group, these parameters did not significantly change during the study. At the last stage of observation, there were statistically significant differences in LAVI and LVEDVi between the compared groups. The dynamics of LV GLS in the compared groups showed multidirectional changes. In the main group, this parameter remained virtually unchanged while in the comparison group, it decreased by ≥15% in 13 patients and reached a statistically significant difference. Clinically pronounced cardiotoxicity and a decrease in the left ventricular ejection fraction (LVEF) developed in 7 of these patients. During the antitumor treatment, the concentrations of the biomarkers remained within the reference values, with the exception of TnI. The greatest differences between the groups were noted in the analysis of mortality. Thus, by the final visit, 13.1% of patients had died in the main group while in the comparison group, mortality was almost two times higher and reached 22.7%. Conclusion    The study demonstrated clinical effectiveness of the cardioprotective therapy in cancer patients at high and very high risk of cardiotoxicity. The patients who did not receive the primary drug prevention of cardiovascular toxicity had a statistically significant impairment of the LV systolic function, an increased number of developed complications, and a higher mortality.

Aim     To monitor the dynamics of biomarkers during chemotherapy, targeted chemotherapy and targeted monotherapy in patients with HER2-positive breast cancer (BC); to analyze the emergence timing of these changes; to compare early biochemical and echocardiographic criteria; and to determine the best time for assessing latent subclinical cardiac dysfunction.Material and methods            Patients with BC (229 women aged 57±11 years) treated sequentially with anthracyclines, a combination of docetaxel and trastuzumab, and trastuzumab monotherapy were examined during three blocks of BC therapy until the development of clinical cardiotoxicity. Time-related changes in high-sensitivity cardiac troponin I, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular (LV) global longitudinal strain (GLS) and LV ejection fraction (EF) (up to 12 speckle-tracking echocardiograms/up to 12 laboratory tests) were analyzed. Clinical cardiotoxicity was defined as a symptomatic decrease in LV EF ≥10% from the baseline value of 54% or more.Results            Clinically significant cardiotoxicity developed in 6.3-10.9% of cases depending on the treatment option for BC. Early manifestations of cardiotoxicity were detected already at 3 weeks after the start of the first course of chemotherapy. For the BC treatment with anthracyclines and targeted chemotherapy with docetaxel and trastuzumab, the markers of clinical cardiotoxicity were high-sensitivity cardiac troponin I, NT-proBNP and GLS LV. For the trastuzumab monotherapy, only GLS LV had a prognostic value. No statistically significant changes in the concentrations of high-sensitivity troponin I and NT-proBNP were found.Conclusion      For timely detection of clinical cardiotoxicity, laboratory tests (high-sensitivity troponin I, NT-proBNP) and echocardiography (GLS LV) are recommended to be performed every 3 weeks before the next course of BC therapy. While doing so, their sensitivity will depend on the treatment option for BC.

Aim     To determine the array of metabolomic profiles and structural and functional parameters of the vascular wall associated with the risk of cardiovascular toxicity of antitumor therapy (ATT) in oncohematological patients.Material and methods            This study included 59 patients, among them 34 patients with lymphomas (non-Hodgkin and Hodgkin lymphoma) and 25 with multiple myeloma. Before and after 3 courses of ATT (anthracyclines, proteasome inhibitors), finger photoplethysmography and transthoracic echocardiography were performed as well as metabolomic profiling (98 metabolites) by high-performance liquid chromatography in combination with tandem mass spectrometry. Statistical analysis of the results included parametric and nonparametric tests, logistic regression, and cross-validation.Results            The study showed that even before the initiation of ATT, cancer patients had signs of endothelial dysfunction and increased vascular wall stiffness (increased aSI, RI, and IO indices), which significantly worsened after the specific treatment. Metabolomic profiling identified a set of metabolites associated with the risk of cardiovascular toxicity, including increased concentrations of amino acids (asparagine, serine, glutamate, glutamine, taurine, citrulline), short-chain acylcarnitines (C18:1 OH-carnitine, C16:1 OH-carnitine, C14OH-carnitine, C2 carnitine), choline metabolism intermediates (TMAO, dimethylglycine, choline), tryptophan metabolites (hydroxyindoleacetic acid, kynurenic acid). Additionally, a logistic regression model was developed based on the analysis of the metabolomic profile, which showed a high prognostic power (AUC = 0.84) for predicting cardiovascular toxicity of ATT.Conclusion      The study identified key metabolites and structural and functional parameters of blood vessels that allow detection of an increased risk of cardiovascular complications of ATT in patients with lymphomas and multiple myeloma before the initiation of a specific treatment. Increased concentrations of amino acids, acylcarnitines, and choline metabolites may serve as an additional risk factor for the onset/progression of cardiovascular complications. The proposed integrative approach, including both metabolomic profiling and non-invasive assessment of the vascular wall condition, opens broad prospects for personalized cardioprotection of cancer patients and more accurate monitoring of the cardiovascular status during ATT.

The development of biological therapeutic agents has provided new opportunities for treating neovascular age-related macular degeneration (nAMD) using humanized monoclonal antibodies (mAbs) targeting vascular endothelial growth factor A (VEGF-A). The emergence of biosimilars of anti-VEGF agents can significantly improve treatment accessibility and its effectiveness by increasing patient adherence. The development of biosimilars involves comparative studies with the original drug to establish equivalence in physicochemical and biological properties, efficacy, and safety. Biosimilar development programs include extensive analytical and preclinical studies to compare structural and functional components with the original bioproduct, and clinical trials are conducted to prove bioequivalence and therapeutic equivalence. The process of development and registration of the biosimilars is strictly regulated and has no significant differences in Russia, the EU and the US. Currently, more than 10 biosimilars of ranibizumab have been approved worldwide, in Russia it is the drug Laxolan (AO GENERIUM). The introduction of a domestic biosimilar of ranibizumab into clinical practice allows reduction of the costs of retinal disease treatment while maintaining the efficacy and safety of antiangiogenic therapy.

Treatment of proliferative diabetic retinopathy (PDR) complications, such as vitreous haemorrhage and tractional retinal detachment, as well as macular involvement, remains a complex multifactorial challenge. The use of angiogenesis inhibitors (AIs) at different stages of patient management is being investigated. In particular, intraoperative use of AIs appears to be pathogenetically justified.

Enhanced cancer treatment efficacy has resulted in a significant increase in the number of cancer survivors after the cure of malignant tumors. However, cardiovascular morbidity, including chronic heart failure, has become the leading cause of death and decreased life expectancy among cancer survivors. This is due, in particular, to the cardiotoxic effects of anticancer drugs and associated factors. Cardioprotective approaches aim to reduce the incidence and severity of cardiotoxicity through the use of cardioprotective agents (e.g., dexrazoxane), liposomal drug delivery systems (e.g., liposomal doxorubicin), and optimization of drug administration schedules. Reducing the cardiotoxicity of cancer treatments is a clinically important goal. Phosphocreatine-based therapy represents a potentially valuable new strategy in this area. In this regard, the study "Multicenter prospective observational study to investigate the experience of using phosphocreatine in combination therapy for heart failure caused by cancer treatment" was initiated. This publication presents the protocol of the observational non-interventional NEOCARD study.

It is known that the advances in cancer treatment leading to increased survival in malignant neoplasms, entail a variety of adverse cardiovascular toxic effects that can be quite serious and even potentially fatal. An important component that influences the degree of cardiotoxicity risk is the patient's clinical and functional state and the cardiovascular history at the time of cancer diagnosis. This information can be used in practice for the cardiovascular screening and clinical and functional evaluation of a patient with a neoplasm before the start of antitumor therapy. After completion of the cardiotoxic therapy, as well as during subsequent follow-up, it is advisable to re-evaluate the risk of long-term cardiotoxicity to determine the frequency and intensity of cardiovascular monitoring. For convenience of calculating the risk of cardiotoxicity in cancer patients undergoing the antitumor treatment, the authors of this article have developed two computer programs that can be used as PC applications (https://disk.yandex.ru/d/NuhzYnicWo9FSw) and on mobile devices (https://disk.yandex.ru/d/uXAriKZ6qhkULA.). These programs facilitate the selection of the correct strategy for the management of cancer patients that is aimed at reducing the likelihood of cardiotoxic complications of the antitumor treatment.

Diabetic macular edema (DME) is a leading cause of visual impairment and blindness among diabetic patients, its prevalence is continuing to increase worldwide. Faricimab, a bispecific antibody, represents a new generation of treatments for DME.

The bony fish Danio rerio (zebrafish) has become one of the important vertebrate model organisms in biomedical cancer research and is used, among other things, for the development of anticancer drugs using xenotransplantation approaches. The ex utero development of zebrafish, optically transparent tissues in the first month of growth, and the immature adaptive immune system during this period greatly facilitate the manipulation of embryos. For highly aggressive cancers where patient survival may be expected to be only a few months, a zebrafish xenograft assay may be the only appropriate method as it requires only four to seven days. Thousands of embryos can be implanted with biopsy tissue from a patient to produce zebrafish xenografts and to use them to screen a large number of drugs and compounds automatically to develop an effective treatment regimen for a specific patient. This review examines the advantages and disadvantages of the zebrafish model in oncology research. The main focus is on the use of zebrafish xenografts to study metastasis and to create avatars in personalized medicine.

Glioblastoma (GB) is the most aggressive malignant brain tumor. To date, there is no optimal treatment approach for this disease. Antidepressants with antitumor effects are one of the new therapeutic directions. A distinctive feature of these drugs is their approval for clinical practice in the treatment of depressive disorders.

To present the four-year experience and the accomplishments of the Scientific and Practical Cardio-Oncology Center of the Sechenov University.

We have previously shown that 5-arylaminouracil derivatives can inhibit HIV-1, herpesviruses, mycobacteria, and other pathogens through various mechanisms. The purpose of this study was to evaluate the potential of 5-arylaminouracils and their derivatives against leukemia, neuroblastoma, and glial brain tumors. 5-Aminouracils with various substituents and their 5'-norcabocyclic and ribo derivatives were screened for cytotoxicity against two neuroblastoma cell lines (SH-SY5Y and IMR-32), K-562 lymphoblastic cells, HL-60 promyeoloblastic cells, and low-passage variants of well-differentiated glioblastoma multiforme (GBM5522 and GBM6138). Cytotoxicity assessment by the standard MTT test showed that most of the compounds lack significant toxicity towards the above cells. However, 5-(4-isopropylphenylamine)uracil and 5-(4-tert-butylphenylamine)uracil exhibited a dose-dependent toxic effect towards the GBM6138 cell line with half-maximal inhibitory concentrations (IC50) of 9 and 2.3 μМ, respectively. Antitumor activity was for the first time demonstrated for compounds of this type and can serve as a starting point for further research.

The most important component of cardio-oncology is the assessment of the risk of development and diagnosis of cardiovascular toxicity of the antitumor therapy, the detection of which is largely based on visualization of the cardiovascular system. The article addresses up-to-date methods of non-invasive visualization of the heart and blood vessels, according to the 2022 European Society of Cardiology Clinical Guidelines on cardio-oncology. Also, the article discusses promising cardiovascular imaging techniques that are not yet included in the guidelines: assessment of coronary calcium using multislice computed tomography and positron emission computed tomography with 18F-labeled 2-deoxy-2-fluoro-d-glucose.

This study analyzes the effectiveness and safety of brolucizumab in the treatment of neovascular age-related macular degeneration (nAMD) in real clinical practice.

A literature search was conducted to review papers on the results of studies of clear cell renal cancer (CCRC) vascularization. Numerous data on the relationship between tumor pathogenesis and its vascularization have been revealed, which indicates the multifactorial nature of CCRC development and the significant role of angiogenesis in this process. It should be taken into account that patients with CCRC may have impaired vessel formation even before tumor development. To evaluate normal and pathologic angiogenesis, a pathohistologic study using immunohistochemistry is certainly necessary. Due to the significant role of angiogenesis in the development and course of CCRC, the use of drugs that suppress the formation of the vascular network in the tumor is relevant and advisable. To date, many drugs have been developed and introduced into clinical practice to inhibit angiogenesis. However, such drugs have not lived up to the expectations placed due to the frequent and rapidly developing drug resistance. Timely detection of pre-tumor and tumor processes, as well as effective treatment of cancer, including CCRC, is possible only with close cooperation between pathomorphologists and oncologists.