Cancer Stem Cell as a Potential Therapeutic Target in Hepatocellular Carcinoma

Roberta      W.C. Pang; Ronnie      T.P. Poon

Abstract

Hepatocellular carcinoma (HCC) is one of the most common human cancers. HCC is a chemoresistant cancer and the current drug therapy has limited efficacy. As a result, the prognosis of HCC patients is generally poor. Recent studies have demonstrated that a subpopulation of cancer cells with stem cell properties, called cancer stem cells (CSCs), are responsible for growth and metastasis of cancer. CSCs characterized by several markers including CD133, CD44, CD90, OV6, Epithelial cell adhesion molecule (EpCAM) and CD13 have been isolated from different human HCC cell lines or specimens. CSCs share many of the signaling pathways found in normal stem cells, such as Wnt, Hedgehog, Notch and Transforming growth factor-beta (TGF-β) pathways. These pathways are involved in self-renewal, differentiation and survival of CSCs. There is evidence of deregulation of these pathways in HCC CSCs. MicroRNAs also play an important role in regulating signaling pathways in HCC, and recent data suggested an important role of microRNA in CSCs of HCC. Therapeutic targeting of CSCs may provide a novel strategy that is more effective than the current drugs targeting the bulk mature cancer cells in treatment of HCC.

Keywords: Cancer stem cells, hepatocellular carcinoma, molecular signaling pathways, targeted therapy, multidrug resistance 1, multidrug resistance-associated protein-1, multidrug resistance-associated protein-3, breast cancer resistance protein, ATP-binding cassette, adenomatous polyposis coli, adenosine triphosphate, bone morphogenetic proteins, chronic myeloid leukemia, cancer stem cells, Delta-like ligands