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Cao. Hepatoma Res 2017;3:241-59 Hepatoma Research
DOI: 10.20517/2394-5079.2017.45
www.hrjournal.net
Viewpoint of Editor-in-Chief Open Access

Cancer Evo-Dev, a novel hypothesis derived

from studies on hepatitis B virus-induced

carcinogenesis

Guang-Wen Cao

Department of Epidemiology, Second Military Medical University, Shanghai 200433, China.

Correspondence to: Prof. Guang-Wen Cao, Department of Epidemiology, Second Military Medical University, 800 Xiang-yin Rd., Shanghai 200433,
China. E-mail: gcao@smmu.edu.cn
How to cite this article: Cao GW. Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis. Hepatoma
Res 2017;3:241-59.
ABSTRACT

Article history: Non-resolving inflammation, which may be maintained by infection, pollution, and metabolic
Received: 9 Oct 2017 stimulants and their interactions with immunogenetic predisposition, provides a fertile field for
Accepted: 21 Oct 2017 cancer development. This is strongly evident in hepatocellular carcinoma. Here, the framework
Published: 27 Oct 2017 of a hypothesis called Cancer Evo-Dev is presented, based on the advances in hepatitis B virus-
induced hepatocarcinogenesis. Several aspects central to this theory are as follows: (1) immune
Key words: imbalance caused by the interaction of immunogenetic predispositions and hepatitis B virus
Inflammation, infection maintains non-resolving inflammation; (2) active inflammation executants promote
hepatitis B virus, mutations in viral and host genomes via disbalancing mutagenic forces including cytidine
mutations, deaminases and mutation-repairing forces including uracil-DNA glycosylases, thus promoting
hepatoma, cancer-related somatic mutations and viral mutations; (3) a small percentage of the cells whose
Cancer Evo-Dev somatic mutations alter the survival signalling adapt to the inflammatory microenvironment,
de-differentiate via demethylating role of cytidine deaminases, and reversely develop into
tumor-initiating cells (TICs); (4) under the cultivation of some factors like POSTN from tumor-
infiltrating fibroblasts and M2 macrophages, TICs acquire the stemness, cancer-stem cells
obtain distinct metastatic and drug-resistant potentials under the selection pressure from distinct
microenvironments; (5) glycolysis persistence in the presence of oxygen provides essential
energy for cell survival and the raw material for DNA synthesis. Thus, cancer development is
characterized by an evolutionary process of “mutation-selection-adaptation”. The framework of
Cancer Evo-Dev can be verified in other cancers. Cancer Evo-Dev lays theoretical foundation
for understanding the mechanisms by which inflammation promotes cancer development, and it
also plays a role in specific prophylaxis, prediction, and targeted treatment of cancers.

NON-RESOLVING INFLAMMATION pain, and swelling” by a Roman physician Cornelius
AND HEPATOCELLULAR CARCINOMA Celsus, is a complex biological response to harmful
stimuli such as infections and tissue damage.
Inflammation can be classified into acute inflammation
Inflammation, firstly characterized as “heat, redness, and chronic inflammation. Acute inflammation, also
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