Irresponsiveness to chemotherapy and small molecule inhibitors can be attributed to a combination of several unique molecular characteristics of FLC tumours: DNAJB1-PRKACA, the oncogenic driver fusion in FLC leads to abnormal activation of protein kinase A and reprogrammed cellular signalling [17], resulting in lower effectiveness of standard cytotoxic drugs. Here, PRKACA is linked to fibrolamellar hepatocellular carcinoma.