The number of cases of melanoma of the skin is steadily increasing every year, which leads to an increase in cases of melanoma associated with pregnancy. To date, there is no convincing evidence of an increased risk of skin melanoma or death from melanoma during pregnancy, however, the treatment of such patients is not an easy task for oncologists. And if surgical treatment of patients with primary melanoma of the skin during pregnancy should be carried out according to modern standards, then the use of targeted drugs and checkpoint inhibitors has been little studied during pregnancy, therefore each individual case requires an individual approach. The article describes the clinical experience of the treatment of melanoma associated with pregnancy at the N.N. Blokhin National Research Medical Center of Oncology.

Uveal melanoma (UM) is the most common primary intraocular tumor. Despite successful treatment of the primary tumor, 50% of patients develop distant metastases. To date, there are no clear standards for choosing the first line of therapy for metastatic UM. The article presents a retrospective analysis of the effectiveness and safety of first-line therapy in 125 patients with metastatic UM who applied to the N.N. Blokhin National Medical Research Center of Oncology in the period from 2020 to 2023.

Uveal melanoma (UM) is the most common intraocular tumor. Despite satisfactory results in the treatment of primary uveal melanoma, almost 50% of patients develop a metastatic lesion. Overall one-year survival in patients with metastatic uveal melanoma reaches 13–40%. Different survival rates are due to the clinical and biological features of uveal melanoma and different prognosis. There is still no standard therapy for metastatic uveal melanoma. Despite all the success achieved in the treatment of patients with metastatic skin melanoma, uveal melanoma is characterized by low sensitivity to drug therapy (whether it is modern immunotherapy with immune checkpoint inhibitors (ICTIs) or targeted or chemotherapy). However, despite the lower efficacy of combined immunotherapy in UM compared with the results for patients with skin melanoma, in recent years its positive role has been noted for UM patients, as well. According to various authors, despite the one-year survival rate of 30-50%, to date, the combination of ipilimumab and nivolumab is recognized as the most effective scheme among other ineffective therapy options. The paper presents the authors’ experience of combined immunotherapy in patients with metastatic uveal melanoma (n = 33) who were treated at the N.N. Blokhin National Medical Research Center of Oncology from 2019 to 2021.

Despite the fact that melanoma is a tumor of visual localization, mortality from skin melanoma remains one of the leading causes of mortality worldwide. Early metastasis of melanoma, even during the initial stages of the tumor process, indicates a high malignant potential of the tumor. Moreover, metastatic melanoma is resistant to current chemotherapy regimens, which is a significant problem today. Progression, resistance to drug therapy of skin melanoma is associated with a population of tumor stem cells, which are characterized by dysregulation of signaling pathways and aberrant phenotypes. The formation of tumor stem cells contributes to their microenvironment. Surface markers expressed by tumor stem cells include transporter proteins that mediate chemoresistance. The study of the microenvironment, the activity of the expressed antigenic determinants makes it possible to understand the processes of chemoresistance formation and to discover (develop) strategies for its overcoming. The article provides an analysis of the literature data on the significance of tumor stem cells in the development of drug resistance of melanoma.

Despite the fact that melanoma is a tumor of visual localization, mortality from skin melanoma remains one of the leading causes of mortality worldwide. Early metastasis of melanoma, even during the initial stages of the tumor process, indicates a high malignant potential of the tumor. Moreover, metastatic melanoma is resistant to current chemotherapy regimens, which is a significant problem today. Progression, resistance to drug therapy of skin melanoma is associated with a population of tumor stem cells, which are characterized by dysregulation of signaling pathways and aberrant phenotypes. The formation of tumor stem cells contributes to their microenvironment. Surface markers expressed by tumor stem cells include transporter proteins that mediate chemoresistance. The study of the microenvironment, the activity of the expressed antigenic determinants makes it possible to understand the processes of chemoresistance formation and to discover (develop) strategies for its overcoming. The article provides an analysis of the literature data on the significance of tumor stem cells in the development of drug resistance of melanoma.

The effectiveness of traditional chemotherapy (with temozolomide, fotemustine, lomustine) alone or in combination with whole brain radiotherapy in melanoma patients with cerebral metastases does not exceed 7–10 % with no significant impact on survival, which is around 2–4 months. Targeted therapy helped to improve survival of patients with disseminated melanoma and BRAF V600 mutations. The use of targeted drugs in patients with brain metastases allows to control the tumor process and to succeed in treatment of cerebral metastases. According to currently available research data and our own results, the effectiveness of targeted therapy with vemurafenib in melanoma patients positive for BRAF V600 mutations with brain metastases reaches 18.0–44.5 % with median survival of 5.3–8.0 months. Evidences suggest that the use of vemurafenib in melanoma patients with brain metastases ensure effective disease control in most of the cases and has a significant advantage comparing to conventional chemotherapy and whole brain radiotherapy. According to the results of these studies vemurafenib can be recommended as a 1st line targeted drug for treatment of melanoma patients with BRAF V600 mutations and brain metastases. Despite the existence of blood-brain barrier and efflux systems, new targeted drugs showed promising results in treatment of brain metastases. Over the last few years we have enhanced our understanding of brain metastasis mechanisms, principles of blood-brain barrier functioning, and ways of cancer drugs penetration into the central nervous system. Targeted therapy is constantly developing and will play an increasing role in treatment of melanoma cerebral metastases in the future with finding of new targets.

The effectiveness of traditional chemotherapy (with temozolomide, fotemustine, lomustine) alone or in combination with whole brain radiotherapy in melanoma patients with cerebral metastases does not exceed 7–10  % with no significant impact on survival, which is around 2–4  months. Targeted therapy helped to improve survival of patients with disseminated melanoma and BRAF V600 mutations. The use of targeted drugs in patients with brain metastases allows to control the tumor process and to succeed in treatment of cerebral metastases. According to currently available research data and our own results, the effectiveness of targeted therapy with vemurafenib in melanoma patients positive for BRAF V600 mutations with brain metastases reaches 18.0–44.5  % with median survival of 5.3–8.0  months. Evidences suggest that the use of vemurafenib in melanoma patients with brain metastases ensure effective disease control in most of the cases and has a significant advantage comparing to conventional chemotherapy and whole brain radiotherapy. According to the results of these studies vemurafenib can be recommended as a 1st line targeted drug for treatment of melanoma patients with BRAF V600 mutations and brain metastases. Despite the existence of blood-brain barrier and efflux systems, new targeted drugs showed promising results in treatment of brain metastases. Over the last few years we have enhanced our understanding of brain metastasis mechanisms, principles of blood-brain barrier functioning, and  ways  of  cancer  drugs penetration into  the  central  nervous system.  Targeted  therapy  is  constantly developing and  will play an increasing role in treatment of melanoma cerebral metastases in the future with finding of new targets.