Fryčová Gabriela

Methylome profiling in cancer cells for identification of bevacizumab response biomarkers

Aberrant regulation at epigenetic level can directly and/or indirectly influence the genetic integrity and gene expression pattern of cells, resulting in the development of various types of disorders, including cancer. The local hypermethylation of tumor-suppressor genes and the global hypomethylation of genomic DNA often occur in human cancers. Multiple DNA methylation changes in the cancer methylome could be associated with the acquisition of drug resistance. At our institute we are currently trying to identify new diagnostic biomarkers, which could be potentially used for better treatment personalization by bevacizumab (Avastin). Bevacizumab is a monoclonal antibody against plasma protein VEGF (vascular endothelial growth factor), which has antiangiogenic effects and is used in clinical practice for treatment of the metastatic colorectal carcinoma (CRC). We assume that genome-wide profiling of DNA methylation could help to identify undiscovered changes associated with good or bad answers to the drug and that it could also help to improve diagnostics of CRC.

Methylome profile changes in cancer cells associated with drug resistance

Aberrant regulation at epigenetic level can directly and/or indirectly influence the genetic integrity and gene expression pattern of cells, resulting in the development of various types of disorders, including cancer. The local hypermethylation of tumor-suppressor genes and the global hypomethylation of genomic DNA often occur in human cancers. Multiple DNA methylation changes in the cancer methylome could be associated with the acquisition of drug resistance. Recently at our institute the cancer cell lines resistant to 2‘-deoxy 5-azacytidine (decitabine) were prepared. Decitabine, a demethylation drug, is used in clinical practice for treatment of hematological malignancies. Since epigenetic therapy is in clinical use or trials for several cancers, efficient methods for epigenetic profiling are needed. Our specific aim is to screen a genome-wide methylation profile of 2-deoxy 5-azacydine resistant cancer cell line HCT116. Our long-term aim is to elucidate the mechanism of drug resistance in cancer cells.