The relation of BRAF inhibitor resistance and HIF 1 expressions in malign melanom cell lines

Malign melanom is the most fatal skin tumour with an increasing incidence. The unresponsiveness to chemotherapy and radiotherapy and rapid resistance to BRAF inhibitors are the main treatment difficulties. Mutations in the MAPK pathway are the main factor in carcinogenesis in melanoma, and the inhibition of resistance to MAPK inhibitors is principal for treatment. Hypoxia defines the low oxygen level in tumour microenviroment. Reactive oxygen species effects the HIF-1α gene and HIF-1α target mechanisms. Hypoxic conditions activates different pathways such as apoptosis and proliferation. The effect of hypoxia on resistance to BRAF inhibitors is still unknown. The determination of resistance mechanisms and definion of possible target molecules will prevent therapy failure and obtain longer survival rates and curability. Key Words: Malign melanoma, BRAF inhibitor, resistance, therapy, HIF inhibitor