Ronde 2014 Internationaal (Innovative Systems Toxicology for Alternatives to Animal Testing):
The liver is a central organ in cancer pathology. Apart from highly prevalent primary cancers (Hepatocellular carcinoma, HCC) the liver is one of the prime sites of metastasis of other cancers. Treatment of cancers requires a balanced combination of cytotoxic agents, which have maximal
oncostatic effects on the tumor and limited toxicity to healthy liver tissue. Predicting therapy response is essential for a personalized medicine approach to cancer. However, conventional culture of primary cancer cells is problematic, requiring xenografts in a large number of mice. Here, we will use innovative culture technology to grow organoids obtained from liver tumor and healthy liver tissue and analyze the impact of known hepatotoxic and/or oncostatic compounds by employing a state-of-the art microfluidics system. By employing a system biology approach we identify key histological, biochemical, genomic and proteomic predictors of optimal on-target and off-target efficacy for personalized treatment of HCC.