Hypothesis of cancer evolution and development (Evo-Dev) and its significance for specific prophylaxis and treatment of cancers
10.3724/SP.J.1008.2015.00349
- Author:
Guang-Wen CAO
1
Author Information
1. Department of Epidemiology, Second Military Medical University
- Publication Type:Journal Article
- Keywords:
Adaptation;
Development;
Evolution;
Inflammation;
Mutation;
Neoplasms;
Selection (genetics)
- From:
Academic Journal of Second Military Medical University
2014;36(4):349-361
- CountryChina
- Language:Chinese
-
Abstract:
Although chronic infection with various pathogens including viruses directly contributes to only approximately 25% of cancers worldwide, chronic inflammation is closely linked to the development, progression and prognosis of most human cancers. In this article the author bring forth a hypothesis termed as “Cancer Evolution-Development” (Cancer Evo-Dev), which is based on our series of studies on the molecular mechanisms of HBV infection-induced hepatocarcinogenesis, gastrointestinal and urological cancers, and world wide advances in this field. The core theory of this hypothesis is: the imbalance or dysfunction caused by the interactions of genetic predispositions and environmental exposures such as viral infection is responsible for the maintenance of chronic non-resolving inflammation. Then non-resolving inflammation promotes cancer occurrence and progression and persists throughout the cancer evolution, which is characterized by a process of “mutation-selection-adaptation”. Under the microenvironment of non-resolving inflammation, pro-inflammatory factors promote mutations in viral or host genomes by trans-activating cytidine deaminases and their analogues or by inducing oxidative stress. The majority of cells acquired somatic mutations and mutated viruses are eliminated in survival competition; only a small percentage of the mutated cells are selected and function as canceHnitiating cells; these mutated cells have altered survival signaling pathways and undergo epithelial-to-mesenchymal transition via epigenetic modification by proinflammatory molecules in an inflammatory microenvironment. The selected cells exhibit the characteristics of “sternness” such as overcoming senescence. robbing nutrition, and proliferating immortally, thus promotes carcinogenesis and invasion. Cancers generally possess the properties of “backward evolution” and “retro-differentiation”, suggesting the indispensability of stem-like signaling pathways in cancer Evo-Dev. This hypothesis of Cancer Evo^Dev is expected to be not only testable in understanding the inherent mechanisms by which inflammation promotes the development of cancers, but also instructive for the prophylaxis and control of cancers in the model of predictive, preventive, personalized, and participatory (P4) medicine.
