Figure 2.

Clinical response to genomic alteration‐matched molecular targeted therapy in two patients with advanced hepatocellular carcinoma (HCC). (A): See Case 1 in Results. A 62‐year‐old man (Patient 6; Table 2) with chronic hepatitis C‐related HCC showed CDKN2A R80* nonsense mutation and CTNNB1 G34V in his circulating tumor DNA (ctDNA). Patient was started on palbociclib (CDK4/6 inhibitor; CDK2A loss of function upregulates CDK4/6) and celecoxib (inhibits CTNNB1‐activated pathway). Results show steep fall in levels of tumor marker des‐gamma carboxy prothrombin. (B): See Case 2 in Results. A 64‐year‐old woman (Patient 4; Table 2) with chronic hepatitis C‐related HCC, after liver transplant, showed MET Y501C missense, TP53 R273C missense, and PTEN L139* nonsense mutation in ctDNA. Patient had been on the mechanistic target of rapamycin inhibitor sirolimus as immunosuppression after liver transplant. Sirolimus suppresses the pathway activated by PTEN mutations. When the MET inhibitor cabozantinib was added, AFP showed a steep decline with stable imaging. MET Y501C ctDNA levels also disappeared at 8 weeks (Fig. 3).

Abbreviation: AFP, alpha fetoprotein.