Despite this evidence mainly poses for the protumoral role of HO-1, controversial anti-tumoral roles of HO-1 has also been reported (i.e. hepatocellular carcinoma, lung mucoepidermoid carcinoma) (38, 39), highlighting the complexity of the HO-1 activity in cancer and suggesting that HO-1 mediated functions are cell type, metabolism and TME dependent (23). The gene discussed is HMOX1; the disease is hepatocellular carcinoma.