Deciphering ZIC2/OCT4 signaling as a vulnerability in liver cancer stem cells

Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed and the second most lethal cancer type, causing an estimated 700,000 deaths in the world, annually (1). In the United States, the incidence of HCC has doubled over the past two decades. The prognosis of the disease is dismal, with only 30% of patients eligible for curative treatments, including liver transplantation or surgical resection, owing to late diagnosis and the presence of underlying liver disease. Although chemotherapy and molecular targeted therapy (sorafenib) is often administered to patients with inoperable HCC as an adjuvant or palliative regimen, tumor recurrence rate is high, partly attributable to the presence of residual self-renewing cancer stems cells (CSCs) that survive initial treatment (2).