Molecular targets for liver cancer therapy: From screening of target genes to clinical trials.
Cancer arises from the accumulation of genetic alterations, and the inactivation of oncogenes, or recovery of suppressor genes, are promising strategies for cancer treatment. Genome-based drug research starts with identification of target genes and is accomplished by exploitation of target-based drugs such as monoclonal antibodies, small molecules and antisense drugs. Recently, clinical trials for treatment of advanced hepatocellular carcinoma (HCC) have been performed, and the effectiveness of sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor and Ras kinase, has been demonstrated. In addition to known target genes, microarray technology has enabled us to constitute novel therapeutic targets, and many researchers have applied this technology in studies of HCC and have identified candidate target genes, validated to affect cell growth. In addition, promoter arrays for whole-genome epigenetic aberration analysis, ChIP-chip analysis using tiling arrays, and high-throughput sequencing systems have been applied to drug discovery. To elucidate the status of therapeutic target genes in vivo, development of diagnostic markers for stratification of patients is a pressing need. Here, we review recent advances in microarray technology for liver cancer, discuss the innovations and approaches to therapeutic target discovery, and present data regarding the outcome of gene target therapy using monoclonal antibodies and molecular diagnostic markers in our laboratory.
Department of Surgery, Teikyo University School of Medicine University Hospital, Mizonokuchi, Kawasaki.
Yutaka
Y
Midorikawa
Yasuyuki
Y
Sugiyama
Hiroyuki
H
Aburatani