TARGEPILIVER · Characterization of Key Epigenetic Targets in Hepatic Fibrosis and Hepatocellular Carcinoma Development. Generation of New Antifibrotic and Antitumoral Drugs.

Characterization of Key Epigenetic Targets in Hepatic Fibrosis and Hepatocellular Carcinoma Development. Generation of New Antifibrotic and Antitumoral Drugs.

"Hepatocellular carcinoma is a malignant tumors that, globally, affect one million new patients each year. For patients with advanced liver cancer the alternative treatment options are very limited because these tumors are poorly sensitive to antitumor drugs. In addition, the dose that can be administered is restricted by the fact that very often they are patients with precarious health by the existence of multiple pathologies and in whom the tumor has developed on a cirrhotic liver, so that there is very low tolerability to the antitumor drugs that the oncologist uses in the attempt to selectively ""poison"" the tumor, being as innocuous as possible for the patient. The expectation for survival of these patients is less than 30% at one year and about half to that at two years. For this reason emerged this project, whose basic idea is that ""not everything that determines tumor development and subsequent behavior, as their response to antitumor drugs, is written in the genes"", but there is a complex cellular machinery, the so-called epigenetic mechanisms, which affects the proper functionality of their expression and that certain elements of that gear can be altered in situations where the initiation of liver cancer is favored, such as chronic liver disease situations. This project aim to identifying such epigenetic changes and their potential enzymes implicated to be used as predictive markers of the risk of developing liver cancer and as molecular targets for novel pharmacological strategies to treat these tumors. The exploration of the epigenetic mechanisms involved in hepatocarcinogenesis processes can open the door to the development of promising new therapies. This has been a pioneering project in the field of hepatic tumor disease, in which, in addition to identifying and characterizing new epigenetic targets, new pharmacological agents potentially capable of preventing and / or treating hepatic fibrosis and HCC have been developed. The weight of chronic liver diseases in Europe has increased greatly in recent decades, assuming a clinical and economic problem, and the prognosis is that they continue to increase in the coming years. Liver cirrhosis along with HCC cause 220,000 deaths a year in the European Union (http://www.easl.eu/_eu-policy/publications), highlighting the need to develop effective therapies. The objectives of this project have been to address this problem with an innovative technology and a multidisciplinary approach and can therefore be susceptible to further clinical development. Our proposal presented two general objectives: i) a comprehensive analysis of the expression and pathological significance of two epigenetic modifiers, the DNA and histone methyltransferases DNMT1 and G9a, in experimental fibrosis, HCC and ii) the development of novel and efficacious DNMT1 and G9a specific inhibitors with a good safety profile, which is critical when treating patients with compromised liver function. These new epigenetic pharmacological tools may be further developed into drugs to prevent chronic liver diseases progression, and to treat HCC alone or in combination with existing drugs. "

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз