Targeting c-Myc as a novel approach for hepatocellular carcinoma

Abstract

Hepatocelluar carcinoma (HCC) is the most lethal cancer in the world. Most HCC over-express c-Myc, which plays a critical role in regulating cellular growth, differentiation and apoptosis in both normal and neoplastic cells. c-Myc is among the most frequently overexpressed genes in human cancers. Overexpression of c-Myc in hepatic cells leads to development of hepatocellular carcinoma. Here, we review the current progress in understanding physiologic function and regulation of c-Myc as well as its role in hepatic carcinogenesis and discuss the association of c-Myc activation in chronic hepatitis B infection and the upregulation of HIF-1/VEGF. We also explore the possibility of treating HCC by inhibiting c-Myc and examine the pros and cons of such an approach. Although this strategy is currently not available in clinics, with recent advances in better drug design, pharmacokinetics and pharmacogenetics, inhibition of c-Myc might become a novel therapy for HCC in the future.

A c-Myc-MicroRNA functional feedback loop affects hepatocarcinogenesis

“…[5][6][7][8][9][10][11][12] Myc is frequently amplified and overexpressed in many different human malignancies, including HCC. 2,3,13,14 Up-regulation of Myc and the reprogramming of transcription signature are critical steps in HCC progression in mice, 15 and Myc is one of the critical genes activated in cancers believed to be caused by infection with HBX virus. 16 Transforming growth factor-b1 and E2F1 may contribute to the promotion and progression of liver carcinogenesis in Myc transgenic mice.…”

Steroid Receptor Coactivator 1 Promotes Human Hepatocellular Carcinoma Progression by Enhancing Wnt/β-Catenin Signaling

“…Overexpression of c-Myc in hepatic cells has been found to lead to HCC formation in mice (28). In this study, protein and mRNA levels of c-Myc were decreased in SRC-1-knockdown cells but increased in SRC-1-overexpressing cells, indicating that SRC-1 positively regulates c-Myc expression.…”

Liposome-mediated Induction of Apoptosis of Human Hepatoma Cells by C-Myc Antisense Phosphorothioate Oligodeoxynucleotide and 5-Fluorouracil

“…The relationship between the c-myc over-expression and liver cancer has been confirmed in some studies (Lin et al, 2010). Recently, gene techniques make it possible for c-myc as a target for liver cancer therapy.…”