Breast cancer (BC) is the most common female cancer and the first leading cause of cancer death in women. Luminal phenotypes represent about 70% of this disease. Treatment for metastatic hormone-dependent HER2-negative breast cancer in most cases involves various lines of endocrine therapy since their sequential use improves overall and relapse-free survival while maintaining a high quality of life. Disease progression during such therapy may be associated with the development of primary or secondary resistance to the treatment. The reason for the secondary resistance is both a mutation of receptors for steroid hormones and activation of new signaling pathways. The study of these mechanisms has led to the creation of highly effective drug combinations for the treatment of hormone-positive HER2-negative metastatic breast tumors. To date, clinical trials of three agents from the group of cyclin-dependent kinases has been developed and successfully completed: palbociclib, ribociclib and abemaciclib. These agents in combination with non-steroidal aromatase inhibitors or estrogen receptor antagonists in randomized clinical trials increased direct treatment efficacy, overall survival and progression-free survival rates. Clinical case of a menopausal patient with metastatic hormone-positive HER2-negative breast cancer with visceral metastases who received successive chemotherapy and a combination of the highly selective oral kinase inhibitor CDK4\6 ribocyclib with the aromatase inhibitor letrozole allowed to achieve a response to therapy for 27 months with CR for 8 months. The safety profile was satisfactory; side effects included grade 2 neutropenia, grade 1 arthralgia, grade 1 hyperglycemia and grade 1 increase in urea which did not had an adverse effect on the patient's quality of life.

Purpose of the study. An analysis of blood levels of TGF-β, TGFR2, TNF-α, TNF-αR1, TNF-αR2, CD44 and MMP9 in patients with various biological subtypes of breast cancer receiving neoadjuvant chemotherapy.Materials and methods. This article presents an analysis of levels of growth and progression factors (TGF-β, TGFR2, TNF-α, TNF-αR1, TNF-αR2, CD44 and MMP9) in the blood of 162 patients with various biological subtypes of locally advanced breast cancer receiving 8 cycles of neoadjuvant chemotherapy.Results. Levels of TGF-β, TGFR2, TNF, TNF-α, TNFR1, TNFR2, CD44, MMP9 in patients with all BC subtypes were high before the treatment. After chemotherapy cycles, the values decreased statistically significantly in all BC subtypes: CD44 decreased by 25.2 %, 30 % and 54.7 % in luminal A, luminal B and TNBC, respectively; TNFα– by 26.2 %, 48.3 % and 50.8 %, respectively; TNFα-R1 – by 52.1 %, 39.2 % and 50.3 % respectively; TNFα-R2 – by 31.7 %, 32.8 % and 41.9 % respectively; MMP9 – 35.3 %, 32.6 % and 43.3 % respectively.Conclusions. We identified a combination of growth and progression factors which determines the chemotherapy sensitivity and resistance in all subtypes of breast cancer; so, a decline in the levels of TGF-β, TNFα, MMP9 and CD44 after neoadjuvant chemotherapy predicts further remission for at least 3 years. On the contrary, stabilization or an increase of these indicators leads to the early tumor progression.

Ростов-на-Дону 2 Больница Christiana Care, г. Ньюарк, штат Делавэр, США РЕЗЮМЕ Ингибиторы иммунных контрольных точек, нацеленные на запрограммированный лиганд гибели клеток PD-L1, стали крупным прорывом в лечении многих онкологических заболеваний. Ниволумаб -это антитело, избирательно блокирующее рецептор PD-1 на поверхности цитотоксических Т-клеток для предотвращения подавления регуляции иммунного ответа. Известно, что ингибиторы иммунных контрольных точек могут вызывать так называемые иммуноопосредованные нежелательные явления, в том числе со стороны эндокринной системы. Сахарный диабет 1 типа является одним из тяжелых редких и потенциально опасных для жизни иммуноопосредованных нежелательных явлений, встречающихся менее чем у 1 % пациентов, получающих лечение ингибиторами иммунных контрольных точек. Хотя общая частота сахарного диабета 1 типа, связанного с ингибитором PD-1, относительно низка, тем не менее он имеет молниеносное течение и может представлять потенциальную угрозу для жизни пациентов, если не будут проведены своевременная диагностика и лечение. Поскольку ингибиторы PD-1 широко используются для лечения многих злокачественных заболеваний, осложнения в виде диабета 1 типа должны привлекать внимание врачей. Кроме того, нельзя не учитывать тот факт, что в ходе лечения врачи должны помогать пациентам лучше распознавать симптомы гипергликемии или диабетического кетоацидоза, что требует тщательного наблюдения за ними во время лечения, регулярного мониторинга уровня глюкозы в плазме крови, оперативного выявления и правильной диагностики и лечения диабета.

Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein‑4 (CTLA‑4) and programmed cell death protein‑1 (PD‑1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.

Introduction. Erythropoietin (EPO) application is a pathogenetic method for anemia correction in cancer patients.The purpose of study. Clinical evaluation of the efficacy and safety of Eralfon® (epoetin alpha) in treatment for anemia in patients with malignant solid tumors during medical anticancer therapy.Materials and methods. We analyzed the data on anemia treatment with Eralfon® in 184 patients with malignant solid tumors receiving various medical anticancer therapies. Eralfon® was injected subcutaneously 12 000 IU 3 times per week or 40 000 IU once a week. Clinical antianemic effect, the time to maximum antianemic effect, adverse events (AE) were analyzed.Results. Patients were stratified by the grade of anemia, stages of treatment, presence of bone metastases, bleeding, previous medical and radiation anticancer therapies, dosage of Eralfon®. The time to effect was shorter in patients under 65. There were no significant differences in efficacy depending on the dosing regimen of Eralfon®. Efficacy was lower in patients with advanced tumors, especially in bone metastases. A history of tumor bleeding, chemotherapy and/or radiation therapy prolonged the period of hemoglobin recovery to normal values. Arterial hypertension and venous thrombosis were the most common AE associated with Eralfon®. Eralfon® 12 000 IU 3 times per week caused less frequent complications, with no cases of ossealgia and myalgia.Conclusion. Eralfon® demonstrated clinical efficacy in treatment for anemia in patients with solid malignant tumors receiving medical anticancer therapy. Dosage of 12 000 IU 3 times per week provided better control of the antianemic effect and adverse events.