Introduction: Malignant melanoma is a type of skin cancer that develops from malignantly transformed melanocytes in the epidermis. Melanoma is one of the most aggressive types of skin cancer. It is also less sensitive to treatment. In addition to standard methods of treatment, new therapeutic approaches are introduced, one being targeted treatment. Target drug or malignant melanoma treatment is Zelboraf (active substance is vemurafenib). Aim: The aim of the master's thesis was to establish whether the combination of radiotherapy and vemurafenib in malignant melanoma with or without mutations in the gene braf reduces cell survival compared to individual exposure to radiotherapy and vemurafenib. Our goal is to determine which types of cells are more sensitive to the combined treatment approach. Methods: In descriptive methods, we reviewed existing relevant peer-reviewed literature in databases. The keywords were: BRAF inhibitors, combination of BRAF inhibitors and radiotherapy, CHL-1 and SK-MEL-28, melanoma. In the empirical part, clonogenic assay was used as a quantitative method. The experiments were performed on two melanoma cell lines SK-MEL-28 in CHL-1 in vitro. Results: We demonstrated a lower survival of SK-MEL-28 cells after exposure to vemurafenib and combination of radiotherapy with vemurafenib than the survival rates of CHL-1 cells. The cytotoxic effect of vemurafenib was observed in SK-MEL-28 cell line, but not CHL-1 cell line. These results show the selective effect of vemurafenib in the presence of braf mutation. After exposure of SK-MEL-28 cells to combination of vemurafenib and radiotherapy, the survival of these cells was lower than after exposure to either treatment alone. The survival of SK-MEL-28 cells at a radiation dose of 2 Gy and the concentration of vemurafenib 0.05 μM was 40%. Discussion and conclusions: The results of this study show that SK-MEL-28 melanoma cells with braf mutation are more sensitive to the combination of vemurafenib and radiotherapy than CHL-1 melanoma cells without braf mutation. Due to the potential synergistic effect of this combined therapeutic approach, it is reasonable to use this combined therapeutic approach for the treatment of malignant melanoma with braf mutation. These results were demonstrated on two cell lines with or without braf mutation in vitro. For a more detailed analysis and possible side effects of the combined vemurafenib and radiotherapy approach for treatment of malignant melanoma, the survival of other malignant melanoma cell lines with or without braf mutation should be evaluated in vitro and in vivo. Experiments with higher concentrations of vemurafenib could provide more detailed treatment observations.
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