恶性肿瘤“五期演变”规律的生物学基础

Biological Basis for’’Five-phase Evolution’’of Malignant Tumors

中国恶性肿瘤发病率、死亡率均居全球首位,中医药在防治恶性肿瘤术后复发、配合放化疗增效减毒、晚期带瘤生存等方面发挥了积极作用。针对肿瘤发生、发展的全过程,结合长期临床实践,本课题组创新提出“虚-寒-毒-闭-衰”五期演变,“郁”贯穿始终,癌毒是核心的中医辨证体系。“五期演变”理论是基于“病证结合”对肿瘤发展不同阶段生理病理状态的总结,该文深入剖析了其生物学基础,提出“虚”重在肿瘤免疫编辑失常,逃避清除;“寒”契合于肿瘤微环境代谢重编程;“毒”表现为肿瘤微环境诱导的癌细胞干性化特征;“闭”与肿瘤新生血管的高渗透长滞留效应(EPR)密切相关;“衰”主因代谢主导权易位所致恶液质;“郁”实质属于激活应激-神经内分泌系统促进肿瘤进展。同时总结提出扶正调衡重塑肿瘤免疫编辑,恢复正向免疫调控“虚”;益气温阳修正肿瘤代谢编程避免“寒”;解毒扶正逆转肿瘤细胞干性抑制“毒”;豁闭清源抑制肿瘤血管生成,调控EPR效应来开“闭”;燮理阴阳从而减缓代谢主导易位,改善无效循环避免“衰”;解郁调气解除神经内分泌应激,防止肿瘤演变疏解“郁”的治疗法则,并佐证以效验方剂,为建立临床防治新体系奠定基础。

China ranks the first in the morbidity and mortality of malignant tumors in the world.Traditional Chinese medicine(TCM)has played a crucial part in preventing recurrence of malignant tumors after surgery,enhancing efficacy and reducing toxicity of radiotherapy and chemotherapy,and promoting the survival of patients with advanced tumors.According to the whole process of tumor occurrence and development and via the long-term clinical practice,we proposed the"deficiency-cold-toxin-blocking-failure evolution theory"of malignant tumors,with depression in the whole process and cancer toxin as the core.The theory is a summary of pathophysiological status at different stages of tumor development based on the disease and syndrome.This paper analyzes the biological basis of the theory.To be specific,we believe that the’’deficiency’’is mainly caused by the tumor immunoediting abnormality and thus the escape of clearance.In addition,the’’cold’’is in line with the metabolic reprogramming of the tumor microenvironment.’’Toxin’’is manifested as the stemness of cancer cells induced by the tumor microenvironment.’’Blocking’’is closely related to the enhanced permeability and retention(EPR)effect of tumor neovasculature.’’Failure’’is exactly the cachexia caused by change of dominant metabolism.’’Depression’’is essentially stress-the accelerated progress of the neuroendocrine system.In combination with clinical practice,we conclude that method of reinforcing healthy Qi and adjusting the balance can help recover tumor immunoediting and restore the immunity to regulate the"deficiency".Moreover,replenishing Qi and warming Yang can correct the tumor metabolic programming to avoid"cold".Removing toxin and reinforcing healthy Qi can reverse tumor cell stemness and thus suppress the’’toxin’’.Eliminating the’’blocking’’source can suppress tumor angiogenesis and help regulate the EPR.Regulating Yin and Yang will help relieve the change of dominant metabolism and futile cycle to avoid’’failure’’.The method of relieving depression and regulating Qi can relieve neuroendocrine stress and prevent tumor progression,thus alleviating the"depression".Moreover,effect of these methods was tested with effective formulas.This study is expected to lay a foundation for the establishment of a new system for the clinical prevention and treatment of malignant tumors.