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Approximately 100 patients are diagnosed with hepatoblastoma each year in the United States, and for the 20% of patients with unresectable or metastatic hepatoblastoma exist limited options. We propose preclinical validation studies of the drug volasertib, which targets the Polo-like kinase 1 (PLK1) oncogene in hepatoblastoma. PLK1 is involved in cell cycle control and is overexpressed in many cancers including hepatoblastoma, but the exact role of PLK1 in hepatoblastoma is unknown. In our preliminary studies we found that volasertib was effective at inhibiting cancer cell growth, but did not affect normal liver cells. We will investigate the underlying role of PLK1 in tumor progression to better understand the mechanism of action for volasertib, as well as test volasertib and the first line chemotherapeutic irinotecan alone and in combination in representative patient-derived xenograft models of hepatoblastoma.
