Neurokinin-1 Receptor Antagonists against Hepatoblastoma.

Abstract

Hepatoblastoma (HB) is the most common malignant liver tumor that occurs during childhood. The prognosis of children with HB is favorable when a complete surgical resection of the tumor is possible, but for high-risk patients, the prognosis is much worse. New anti-HB strategies must be urgently developed. The undecapeptide substance P (SP) after binding to the neurokinin-1 receptor (NK-1R), regulates cancer cell proliferation, exerts an antiapoptotic effect, induces cell migration for invasion/metastasis, and triggers endothelial cell proliferation for neoangiogenesis. HB samples and cell lines overexpress NK-1R (the truncated form) and SP elicits HB cell proliferation. One of these strategies could be the use of non-peptide NK-1R antagonists. These antagonists exert, in a concentration-dependent manner, an antiproliferative action against HB cells (inhibit cell proliferation and induce the death of HB cells by apoptosis). NK-1R antagonists exerted a dual effect in HB: Decreased both tumor volume and angiogenic activity. Thus, the SP/NK-1R system is an important target in the HB treatment and NK-1R antagonists could act as specific drugs against HB cells. In this review, we update and discuss the use of NK-1R antagonists in the treatment of HB.