Potential druggable mutations can be identified by circulating tumor DNA in advanced hepatocellular carcinoma


In patients with hepatocellular carcinoma (HCC), imaging can accurately diagnose the disease, so that biopsy isn’t often performed. The other issue is the risk associated with biopsy. HCC is a highly vascular tumor, so performing biopsy carries an increased risk of bleeding. The demand for getting disease information is largely unmet. Circulating tumor DNA (ctDNA) is a good material for cancer genetic information detection. In this study, next generation sequencing (68 genes) was used to detect ctDNA in 14 patients with advanced HCC. 12 patients (78%) had at least one actionable mutation. Five patients received matched therapy, and two had clinical benefits. The first patientone with CDKN2A R80* nonsense mutation and CTNNB1 G34V missense mutation received a CDK4/6 inhibitor (palbociclib) and a COX-2 inhibitor (celecoxib). In two months, the des-gamma-carboxy prothrombin (DCP) declined 84% from the baseline. The second patientone with MET Y501C missense mutation, TP53 R273C missense mutation and PTEN L139* nonsense mutation received a MET inhibitor (cabozantinib) and a mTOR inhibitor (sirolimus). Within one month, the alpha fetoprotein (AFP) declined 63% from the baseline. The data indicated that ctDNA is an alternative tool for getting genetic information, and have the potential for targeted treatment selection in advanced HCC.

Ikeda S, et al, Oncologist, 23(5):586-593, 2018

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