Search

Hepatocellular carcinoma is a common malignancy globally with increasing incidence and significant cancer mortality. Delayed detection leads to a poor prognosis with median survival of < 10 months. Only very few patients qualify for a resection or transplantation. Even local treatments are only useful in very few selected patients. No strong evidence exists on beneficial effect of any chemotherapy, hormonal therapy, or immunotherapy in advanced HCC-patients. Thus finding effective systemic treatments for non-resectable HCC has become a great challenge. HTI-286 is a synthetic analogue of hemiasterlin and depolymerises microtubules. In several human xenograft models HTI-286 has shown significant antitumor activity. We have analyzed antitumor effect of HTI-286 alone or in combination with CCI779 on hepatic tumor cells in an in-vitro and in-vivo model. Proliferation of all hepatic tumor cells (MH, Hep3B und HepG2) was inhibited in-vitro. Primary human hepatocytes were not affected by HTI-286. A significant tumor reduction was seen in-vivo in the HTI and HTI/ CCI779 group. HTI inhibits tumor cell proliferation in-vitro and in-vivo. CCI779 seems to have an additive effect on tumor reduction. HTI is to be considered as a promising drug in the treatment of advanced HCC.