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Emerging role of insulin-like growth factor-binding protein 7 in hepatocellular carcinoma

Authors Akiel M, Rajasekaran D, Gredler R, Siddiq A, Srivastava J, Robertson C, Jariwala N, Fisher P, Sarkar D

Received 7 January 2014

Accepted for publication 3 February 2014

Published 26 March 2014 Volume 2014:1 Pages 9—19


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Maaged Akiel, Devaraja Rajasekaran, Rachel Gredler, Ayesha Siddiq, Jyoti Srivastava, Chadia Robertson, Nidhi Himanshu Jariwala, Paul B Fisher, Devanand Sarkar

Department of Human and Molecular Genetics, Massey Cancer Center, VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

Abstract: Hepatocellular carcinoma (HCC) is a vicious and highly vascular cancer with a dismal prognosis. It is a life-threatening illness worldwide that ranks fifth in terms of cancer prevalence and third in cancer deaths. Most patients are diagnosed at an advanced stage by which time conventional therapies are no longer effective. Targeted molecular therapies, such as the multikinase inhibitor sorafenib, provide a modest increase in survival for advanced HCC patients and display significant toxicity. Thus, there is an immense need to identify novel regulators of HCC that might be targeted effectively. The insulin-like growth factor (IGF) axis is commonly abnormal in HCC. Upon activation, the IGF axis controls metabolism, tissue homeostasis, and survival. Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein of a family of low-affinity IGF-binding proteins termed “IGFBP-related proteins” that have been identified as a potential tumor suppressor in HCC. IGFBP7 has been implicated in regulating cellular proliferation, senescence, and angiogenesis. In this review, we provide a comprehensive discussion of the role of IGFBP7 in HCC and the potential use of IGFBP7 as a novel biomarker for drug resistance and as an effective therapeutic strategy.

Keywords: HCC, IGFBP7, gene therapy, angiogenesis, senescence, apoptosis

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