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Lin et al. Hepatoma Research 2018;4:26 Hepatoma Research
DOI: 10.20517/2394-5079.2018.27

Review Open Access

Hypoxic microenvironment and hepatocellular
carcinoma treatment

Ci-Ai Lin, Lin-Lin Chang, Hong Zhu, Qiao-Jun He, Bo Yang
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou
310058, Zhejiang, China.

Correspondence to: Dr. Bo Yang, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences,
Zhejiang University, 866# Yuhangtang Rd, Hangzhou 310058, Zhejiang, China. E-mail: yang924@zju.edu.cn; Dr. Qiao-Jun He, Zhejiang
Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, 866# Yuhangtang Rd,
Hangzhou 310058, Zhejiang, China. E-mail: qiaojunhe@zju.edu.cn
How to cite this article: Lin CA, Chang LL, Zhu H, He QJ, Yang B. Hypoxic microenvironment and hepatocellular carcinoma treatment.
Hepatoma Res 2018;4:26. http://dx.doi.org/10.20517/2394-5079.2018.27
Received: 22 Mar 2018 First Decision: 17 May 2018 Revised: 9 Jun 2018 Accepted: 9 Jun 2018 Published: 29 Jun 2018

Science Editor: Guang-Wen Cao Copy Editor: Jun-Yao Li Production Editor: Huan-Liang Wu

Abstract
Hepatocellular carcinoma (HCC) is one of the most rapidly growing and prevalent cancers in the whole world. The
characterized hypoxia region inside the HCC tumors has been recently found as the key driver of HCC malignance
and treatment failure, leading to a variety of hypoxia-related biological consequences including angiogenesis,
metastasis, metabolism deregulation and drug resistance, which ultimately resulted in treatment failure of HCC.
This review will summarize the signaling pathways involved in hypoxia-mediated malignance of HCC and discuss
current advances of hypoxia-targeted therapies.

Keywords: Hepatocellular carcinoma, anti-cancer drugs, hypoxia-targeting strategie

INTRODUCTION
Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, with a high mortality of
[1,2]
5-year survival rate less than 10% . There are various etiologies implicated in development of HCC,
[3,4]
including infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) , chronic infection, and alcohol
[5]
consumption . According to the Barcelona Clinic Liver Cancer (BCLC) staging, HCCs can be classified into
[1]
five stages with each receiving different treatments . Effective therapeutic options include liver resection
[1]
and liver transplantation, ablation and chemoembolization . However, for patients often diagnosed with
[1]
advanced, unresectable or metastatic HCC, chemotherapeutic treatment would be the only option . Yet, as
[6]
reported, significant drug resistance in these patients ultimately resulted in treatment failure .
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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