In the Western world, metabolic diseases and infections with hepatitis C are the most common causes of hepatocellular carcinoma (HCC). The team led by Wolfgang Mikulits, Head of the Tumour Progression and Metastasis Research Group at the MedUni Vienna’s Institute of Cancer Research (ICR) and member of the Comprehensive Cancer Center (CCC) Vienna, investigated the role of the AXL receptor tyrosine kinase in the context of liver cancer as part of a study. Says Mikulits: “Until now, the function of AXL had been barely investigated at all, which is astonishing since this receptor is shown to have been activated in more than 50 per cent of all HCC patients.”
AXL changes signalling pathways The researchers were able to demonstrate that the expression (presence) and activation of AXL lead to a diversion of signalling pathways, enabling the migration and metastasis of liver cancer cells. As a result, AXL, after binding a 14-3-3 adapter protein, is able to influence the extremely important transforming growth factor (TGF) beta signalling pathway in such a way that it only causes the invasion and metastasis of HCC cells. In contrast to this, AXL inhibits the anti-oncogenic function of TGF-beta. AXL is therefore the crucial key factor in the aggressive development of hepatocellular carcinoma. The analyses of patient samples confirm the experimental data, according to which the high expression of AXL and the activation of TGF-beta is related to a greatly reduced life expectancy for HCC patients.
New therapeutic approach The discovery that this central switching centre for tumour development promotes it instead of inhibiting it opens up new possibilities for the effective treatment of HCC. By using a highly specific AXL inhibitor, the progression of the cancer could be prevented in a large number of patients. At the University Department of Internal Medicine I at the MedUni Vienna and the Vienna General Hospital, Director Christoph Zielinski has set the course for the first clinical testing phase on HCC patients.