从“神不使”探讨EGFR-TKI耐药形成机制及延缓耐药策略

Discussion on the mechanism of EGFR-TKI drug resistance and the strategy of delaying drug resistance from‘god does not make'

表皮生长因子受体(EGFR)-酪氨酸激酶抑制剂(TKI)是目前EGFR突变的恶性肿瘤患者重要治疗选择之一,耐药问题的出现限制了它的应用,中医药在干预耐药形成中发挥着重要作用,但其作用机制尚不清楚。“神不使”是指生命活动的调控和主宰机制失常,可能为导致耐药的根本原因。文章分析恶性肿瘤患者情绪不良、依从性差等心理因素,以及EGFR-TKI药性属热,过用伤营卫等身体因素,共同导致“神不使”,致“神”无法再调动EGFR-TKI之气到达病所,或为EGFR-TKI耐药形成的核心机制。基于“神不使而病不愈”理论,提出解郁节劳、温阳益气、滋阴养血、护胃醒脾4种治法以养精全神,进而延缓EGFR-TKI耐药发生,以期为临床应用中医药联合EGFR-TKI治疗恶性肿瘤提供有益参考。

Epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)is one of the important treatment options for malignant tumor patients with EGFR mutation.The emergence of drug resistance limits its application.Traditional Chinese medicine(TCM)plays an important role in interfering the formation of drug resistance,but its mechanism is not clear.‘God does not make'refers to the abnormal regulation and control mechanism of life activities,which may be the root cause of drug resistance.This paper analyzes the psychological factors such as poor mood and poor compliance of patients with malignant tumor,as well as physical factors such as heat of EGFR-TKI and overuse of injury camp and health,which jointly lead to‘God does not make',so that‘god'can no longer mobilize the qi of EGFR-TKI to reach the disease,which may be the core mechanism of EGFR-TKI drug resistance.Based on the theory of"sickness cannot be cured without god's help",this paper puts forward four treatment methods of relieving depression and saving labor,warming yang and replenishing qi,nourishing yin and nourishing blood,protecting stomach and awakening spleen to nourish essence,and then delaying the occurrence of EGFR-TKI drug resistance,in order to provide useful reference for clinical application of TCM combined with EGFR-TKI in the treatment of malignant tumor.