Integrative Biology

Biography

Biography: Ewa Maj

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Due to lack of early symptoms patients are diagnosed with advanced stage of the disease. Growing tumors promotes angiogenesis inside malignant tissue, what next results in metastatic potential and poor prognosis. Tumor angiogenesis is one of the targets for anticancer therapy developed today. Malignant cells, including lung cancer cells, release many growth factors that are involved in tumor angiogenesis. Blocking signal transduction pathway of VEGF, main angiogenicfactor, by for example VEGF receptor inhibitors or anti-VEGF monoclonal antibodies results in endothelial cells apoptosis what in turn blocks angiogenesis. Recently it was discovered, that tumor suppressor p53 protein is involved in controlling tumor vascularization. In cancer tissue samples obtained from patients with lung cancer,immunohistochemical analysis showed that mutant p53 correlated with higher VEGF expression. In our study we decided to combine some tyrosine kinase inhibitors(TKI) withcytostatics: cisplatin anddocetaxeland also calcitriol analog as a proposed treatmentin non-small cell lung cancer (NSCLC) model. The research focused on combined effect of above mentioned drugs towards proliferation of lung cancer and endothelial cells and the VEGF production by cancer cells in vitro. The mechanism of observed downregulation of VEGF expression in lung cancer cells after exposure to combination of TKI with cytostaticswas explored.