Moving Targets in Hepatocellular Carcinoma: Hepatic Progenitor Cells as Novel Targets for Tyrosine Kinase Inhibitors

Abby Siegel

doi:10.1053/j.gastro.2008.07.036

Abstract

Moving Targets in Hepatocellular Carcinoma: Hepatic Progenitor Cells as Novel Targets for Tyrosine Kinase Inhibitors

Highlights

It is known that several tumor suppressors or proto-oncogenes are mutated in Hepatocellular carcinoma (HCC), including p53, Rb and IGF. 4 In addition, many intracellular signaling pathways have been shown to contribute to HCC growth
At the 2007 American Society of Clinical Oncology meeting, sorafenib, an oral multikinase inhibitor of raf kinase, VEGFR2, VEGFR3 and PDGFR-β kinases, was reported to lead to an improvement in overall survival by about 3 months when compared with placebo in a large, randomized trial of advanced HCC patients.[6]
Knight and colleagues in this issue of Gastroenterology suggest another possible mechanism of antitumor activity using imatinib for HCC by targeting presumptive hepatic progenitor cells.[15]

Summary

Introduction

In addition to direct targeting of tumor-related growth pathways, other paradigms for treating cancer have emerged using tyrosine kinase inhibitors. One of these includes targeting the tumor “stroma,” including endothelial cells and fibroblasts which support cancer cell growth.

Results

Conclusion