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Prognostic markers and putative therapeutic targets for hepatocellular carcinoma

Frau, Maddalena and Biasi, Fiorella and Feo, Francesco and Pascale, Rosa Maria (2010) Prognostic markers and putative therapeutic targets for hepatocellular carcinoma. Molecular Aspects of Medicine, Vol. 31 (2), p. 179-193. eISSN 1872-9452. Article.

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DOI: 10.1016/j.mam.2010.02.007

Abstract

Hepatocellular carcinoma (HCC) is the fifth most frequent human cancer and a fatal disease. Therapies with pharmacological agents do not improve the prognosis of patients with unresectable HCC. This emphasizes the need to identify new targets for early diagnosis, chemoprevention, and treatment of the disease. Available evidence indicates that clinical outcome of HCC could reflect the genetic predisposition to cancer development and progression. Numerous loci controlling HCC progression have been identified in rodents. In this review, we describe results of recent studies on effector mechanisms of susceptibility/resistance genes, responsible for HCC progression, aimed at identifying new putative prognostic markers and therapeutic targets of this tumor. Highest c-myc amplification and overexpression, alterations of iNOS crosstalk with IKK/NF-kB and RAS/ERK signaling, ubiquitination of ERK and cell cycle inhibitors, and deregulation of FOXM1 and cell cycle key genes occur in rapidly progressing dysplastic nodules and HCC, induced in genetic susceptible rat strains, compared to the lesions of resistant rats. Notably, alterations of these mechanisms in human HCC subtypes with poorer or better prognosis, are similar to those present in genetically susceptible and resistant rats, respectively, and function as prognostic markers and therapeutic targets. Attempts to cure advanced HCC by molecular therapy directed against specific targets led to modest survival benefit. Thus, efforts are necessary to identify and test, in pre-clinical and clinical studies, new therapeutic targets for combined molecular treatments of HCC. They may take advantage from the comparative analysis of signal transduction in HCCs differently prone to progress, in rats and humans.

Item Type:Article
ID Code:5649
Status:Published
Refereed:Yes
Uncontrolled Keywords:Hepatocarcinogenesis, prognostic markers, therapeutic targets, signal transduction, genetic predisposition
Subjects:Area 06 - Scienze mediche > MED/04 Patologia generale
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Pergamon / Elsevier
eISSN:1872-9452
Copyright Holders:© 2010 Elsevier
Additional Information:Special issue on Molecular mechanisms and new therapeutic targets in human carcinogenesis, edited by Francesco Feo and Giuseppe Poli
Deposited On:09 Mar 2011 09:26

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