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慢性炎症恶性转化是绝大多数癌症发生发展的共有过程。根据基因组学、体细胞变异/表观遗传影响的信号通路和流行病学等研究形成的证据链,笔者提出了癌症进化发育(cancer evolution-development,Cancer Evo-Dev)的新理论框架:先天免疫遗传与后天环境暴露的交互作用引发并维持了慢性非可控性炎症;炎症分子持续反式激活胞苷脱氨酶,该类酶被激活后发挥炎-癌转化桥梁的作用,诱导产生大量体细胞突变;绝大多数变异细胞被生存竞争淘汰,少数则通过体细胞变异和炎症相关表观遗传修饰改变了信号转导模式,经去分化过程而获得干性特性,通过并适应了炎症微环境的选择,发展成癌症起始细胞;这一过程遵循“变异-选择-适应”的进化规律。癌症进化发育学的提出不仅有利于阐明炎-癌转化的一般规律,而且对癌症的特异性预防、预测和靶向治疗有重要指导作用。
Malignant transformation of chronic inflammation is the most common process of cancer development. According to the evidence chain formed by the studies of genomics, somatic mutation / epigenetic signal pathways and epidemiology, the author puts forward a new theoretical framework of cancer evolution-development (Cancer Evo-Dev): innate immunity Interactions between heredity and acquired environment lead to and maintain chronic non-controllable inflammation; inflammatory molecules continue to transactivate cytidine deaminase, which activates and then acts as a bridge of inflammation-cancer transformation and induces the production of large numbers of Cell mutation; the vast majority of mutant cells were eliminated by competition for survival, and a few changed the signal transduction mode by somatic mutation and epigenetic modification related to inflammation, and obtained the dryness characteristics through dedifferentiation process, passed and adapted to the inflammatory microenvironment The development of cancer initiating cells; this process follows the evolutionary law of “mutation-selection-adaptation”. Advances in the development of cancer evolution not only help to clarify the general rules of inflammation-cancer transformation, but also have an important guiding role in the prevention, prediction and targeted therapy of cancer.