Liver cancer remains a global challenge of healthcare, with the incidence growing worldwide. According to various authors, over 1 million patients will be diagnosed with liver cancer each year by 2025. The molecular pathogenesis of HCC varies with respect to genotoxic lesions and aetiologies. Although our understanding of the HCC pathophysiology and drivers tends to improve, it is still distant from translation into clinical practice. About 25 % of HCC cases are associated with variant mutations. HCC pathophysiology is a complex multi-step process. The interaction of various factors underlies the early stages of malignant hepatocyte transformation towards the development of HCC. Overall, about 20–25 % of HCC patients have at least one potential driver mutation. Obesity should also be noted as being associated with a higher risk of HCC and various other cancers. Despite many issues in the HCC pathogenesis being already known, the unresolved questions remain. Modern molecular genetic diagnostics and animal modelling of malignant tumours are expanding our horizons of knowledge in this field.

Endometrial cancer is one of the most common gynaecological cancers in both the United States and the Russian Federation, and the rate continues to rise. Although early-stage endometrial cancer is associated with a favourable 5-year survival rate (96%), this rate in patients with distant metastases accounts for only 18%. A combination of paclitaxel and carboplatin is standard first-line therapy for advanced, recurrent and metastatic endometrial carcinoma. Pembrolizumab, a monoclonal antibody targeting the programmed death-1 receptor, is approved for therapy of metastatic solid tumors with high microsatellite instability that have progressed aft er previous therapy and have no alternative treatment options. Lenvatinib is an oral multikinase inhibitor that blocks vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor alpha, RET and KIT. Phase II and III studies (KEYNOTE-146/ Study111 and KEYNOTE-775) on the combination of lenvatinib and pembrolizumab in advanced endometrial carcinoma, irrespective of MMR and MSI status, have shown new potential for the treatment of this pathology. Th e results obtained, including progression-free and overall survival, allow the combination of lenvatinib and pembrolizumab to be considered a new standard for the treatment of this pathology.

Background. PARP inhibitor olaparib shows encouraging results in the treatment of patients with BRCA-associated tumors. The detection of new tumors associated with abnormalities of the BRCA gene, also can lead to the expansion of PARP inhibitors application. The application of PARP inhibitors improved treatment outcomes for ovarian, breast, prostate and pancreatic cancers in comparison with standard drug therapy regimens, demonstrating the moderate toxicity profile. All this makes olaparib the significant option in planning the tactics of treatment of this category of patients. Aim. Assess the efficacy of olaparib in real clinical practice conditions in our region and to demonstrate the clinical experience accumulated in the regional clinical oncology dispensary. Materials and methods. We analyzed the cases of the treatment with olaparib in the Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Bashkortostan. The study included 79 patients. Results. Median progression-free survival reached 12 months and the best response was the stabilization of the disease among patients receiving olaparib. Median progression-free survival was 6 months and the best response was the stabilization of the disease among the patients treated with olaparib during Re-Challenge regimen. Conclusion. Olaparib applying in real clinical practice demonstrated satisfactory results.

Randomized clinical trials and actual clinical practice differsignificantly. Evidence-based medicine develops new agents referring to, primarily, pharmaceutical findings, preclinical studies and, most importantly, randomized clinical trials. Hepatocellular carcinoma is the most common primary malignancy of the liver, and one of the main causes of fatal outcomes among cancer patients worldwide, including in the Asia-Pacific region, with an estimated 800,000 deaths annually. For more than 10 years, sorafenib, a tyrosine kinase inhibitor, was the only authorized treatment for advanced hepatocellular carcinoma. The next stage in the development of drug therapy for hepatocellular carcinoma involved immune checkpoint inhibitors. The combination of atezolizumab with bevacizumab in the phase III trial (IMbrave150) improved outcomes of advanced hepatocellular carcinoma, such as overall survival and progression-free survival (6.8 versus 4.3). The paper presents the trials of atezolizumab and bevacizumab combination, demonstrates comparable data on the treatment of patients with HCC in real clinical practice and data on the phase III IMbrave150. To further analyze the efficacy of the combination of atezolizumab and bevacizumab, prospective clinical trials should include heterogeneous patient groups.