INHIBITION OF THE LIVER ENRICHED PROTEIN FOXA2 FOR THE TREATMENT OF COLORECTAL LIVER METASTASES

摘要

The invention is directed to the use of substances decreasing the expression or activity of Foxa2 and/or increasing the expression or activity of HNF6 in the treatment of tumor cells, in particular of primary or secondary liver malignancies, preferably of colorectal liver metastases. Areas of application are the life sciences and the pharmaceutical industry. In one aspect, the invention provides a medicament and medication, compositions, and substances, and the use of said compositions and substances for preventing and treating liver metastases, in particular metastases in the liver made up of or derived from non-hepatic tumor cells, preferably colorectal liver metastases. The invention is based on the surprising finding that siRNA-mediated gene silencing recovers HNF6 activity in Colorectal adenocarcinoma cells and that transfection of a plasmid encoding HNF6 significantly reduces the proliferation of both Colorectal adenocarcinoma cells and Human hepatocellular liver carcinoma cells and results in cell cycle arrest of said cells. In particular, the invention therefore relates to a composition that - decreases or inhibits the expression or activity of Foxa2 and/or increases the expression or activity of HNF6 for use in the treatment of tumor cells and as a medicament (or for the use as a medicament, respectively) for the prevention or treatment of liver metastases, in particular metastases in the liver made up of or derived from non-hepatic tumor cells, more particular for preventing or treating colorectal liver metastases, or for the prevention or treatment of colorectal adenocarcinoma or for the prevention or treatment of hepatocellular carcinoma.