Panobinostat plus vincristine/irinotecan shows potential in treatment-refractory hepatoblastoma

Use of panobinostat in combination with vincristine and irinotecan chemotherapy provides effective tumour response in models developed from patients with high-risk, relapsed, and treatment-refractory hepatoblastoma (HB), according to a study.

A team of investigators analysed RNA sequencing, microarray, NanoString, and immunohistochemistry data of HB samples for histone deacetylase (HDAC) class expression. They used patient-derived spheroids (PDSp) to screen combination chemotherapy with the HDAC inhibitor panobinostat.

The investigating team also developed patient-derived xenograft (PDX) mouse models, which were treated with the combination therapy showing the highest efficacy in the PDSp drug screen.

HDAC RNA and protein expression in HB tumours were elevated relative to normal livers. Treatment with panobinostat (IC₅₀ of 0.013-0.059 μM) induced robust in vitro effects and correlated with lower cell viability relative to other HDAC inhibitors. The PDSp drug screen displayed the highest level of cell death with panobinostat plus vincristine/irinotecan (VIP).

All four models showed response to VIP therapy with a tumour size reduction compared with placebo. After 6 weeks of treatment, two models exhibited necrotic cell death, with reduced Ki67 expression, serum alpha fetoprotein, and tumour burden relative to vincristine/irinotecan- and placebo-treated groups.

“Patients with treatment-refractory HB have limited treatment options with survival rates of less than 50 percent,” the investigators said. “Our manuscript demonstrates that combination therapy with vincristine, irinotecan, and panobinostat reduces the size of high-risk, relapsed, and treatment-refractory tumours.”