title: Cancer Evolution-Development: experience of hepatitis B virus-induced hepatocarcinogenesis.
abstract: Here, we present the basic concept and theoretical framework of a scientific hypothesis called Cancer Evolution-Development ("Cancer Evo-Dev"), based on our recent studies of the molecular mechanisms by which chronic infection with the hepatitis B virus induces hepatocarcinogenesis, together with related advances in that field. Several aspects central to our hypothesis are presented: ■ Immune imbalance-caused by the interaction of genetic predispositions and environmental exposures such as viral infection-is responsible for the maintenance of chronic non-resolving inflammation. Non-resolving inflammation promotes the occurrence and progression of cancers, characterized by an evolutionary process of "mutation-selection-adaptation" for both viruses and host cells.■ Under a microenvironment of non-resolving inflammation, proinflammatory factors promote mutations in viral or host genomes by transactivation of the expression of cytidine deaminases and their analogues. Most cells with genomic mutations and mutated viruses are eliminated in the competition for survival in the inflammatory microenvironment. Only a small percentage of the mutated cells that alter their survival signal pathways and exhibit the characteristics of "stem-ness" can survive and function as cancer-initiating cells.■ Cancers generally develop with properties of "backward evolution" and "retro-differentiation," indicating the indispensability of stem-like signal pathways in the evolution and development of cancers. The hypothesis of Cancer Evo-Dev not only lays the theoretical foundation for understanding the mechanisms by which inflammation promotes the development of cancers, but also plays an important role in specific prophylaxis, prediction, early diagnosis, and targeted treatment of cancers.
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, P.R.C.
authors.forename: W B
authors.initials: WB
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, P.R.C.
authors.forename: J F
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, P.R.C.
authors.forename: Y
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, P.R.C.
authors.forename: G W
authors.initials: GW
authors.lastname: Cao
keywords: Hepatocarcinogenesis; evolution; hepatitis B virus; inflammation; mutations