Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Jan;100(1):1-8.
doi: 10.1111/j.1349-7006.2008.01006.x. Epub 2008 Nov 25.

Molecularly targeted therapy for hepatocellular carcinoma

Shinji Tanaka  1 , Shigeki Arii
Affiliations
Review

Molecularly targeted therapy for hepatocellular carcinoma

Shinji Tanaka et al. Cancer Sci. 2009 Jan.

Abstract

Accumulated understanding of the molecular pathways regulating cancer progression has led to the development of novel targeted therapies. Hepatocellular carcinoma (HCC) remains a highly lethal disease that is resistant to conventional cytotoxic chemotherapy and radiotherapy. Unlike conventional chemotherapy, molecular-targeted agents offer the potential advantages of a relatively high therapeutic window and use in combination with other anticancer strategies without overlapping toxicity. It is hoped that these drugs will become valuable therapeutic tools within the multimodal approach to treating cancer. A recent clinical trial revealed an oral multikinase inhibitor, sorafenib, as the first agent that has demonstrated improved overall survival in patients with advanced HCC. The present review summarizes molecular abnormalities of HCC with a focus on clinical studies, and current status as well as problems of the targeted strategies for HCC.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Molecular targets in the (a) epidermal growth factor (EGF) and EGF receptor (EGFR) family, (b) vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) family, and (c) insulin‐like growth factor (IGF) and IGF receptor (IGFR). Targeted agents are indicated by arrows.
Figure 2
Figure 2
Molecular targets in mitogen‐activated protein kinase (MAPK) and phosphatidylinositol‐3 kinase (PI3K) signal transduction pathways stimulated by receptor tyrosine kinases (RTK). Targeted agents are indicated by arrows. GF, growth factor; SOS, sun of sevenless; MEK, MAPK/extracellular regulated kinase kinase; PTEN, phospharase and tensin homologue; PDK, phosphoinositide‐dependent kinase; IKK, IκB kinase; mTOR, mammalian target of rapamycin.
Figure 3
Figure 3
(a) The mitosis phase of the cell cycle. Localization of Aurora kinases is shown. Green spots, the centrosome protein Aurora kinase A; red spots, the chromosomal passenger Aurora kinase B. (b) The concept of mitotic catastrophe, induced by inhibition of Aurora kinases in cancer cells. Under abnormalities in each checkpoint system, p53‐independent death is induced as senescence‐like polyploidy without successfully completing mitosis.
See this image and copyright information in PMC

References

    1. Llovet JM, Ricci S, Mazzaferro V et al . Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378–90. - PubMed
    1. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006; 6: 674–87. - PubMed
    1. Ince N, Wands JR. The increasing incidence of hepatocellular carcinoma. N Engl J Med 1999; 340: 798–9. - PubMed
    1. Arii S, Yamaoka Y, Futagawa S et al . Results of surgical and nonsurgical treatment for small‐sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan. Hepatology 2000; 32: 1224–9. - PubMed
    1. Tanaka S, Sugimachi K, Maehara S et al . Oncogenic signal transduction and therapeutic strategy for hepatocellular carcinoma. Surgery 2002; 131: S142–7. - PubMed

MeSH terms