Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two main subtypes of liver cancer. Lars Zender and colleagues now show that the tumour microenvironment determines which type of liver cancer develops. They find that transformed hepatocytes give rise to ICC when surrounding hepatocytes undergo necroptosis, whereas hepatocytes transformed with the same oncogenes develop into HCC when surrounded by hepatocytes that are undergoing apoptosis. Mechanically, the authors link this to differences in the cytokine milieu and gene expression.
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