RESUMO
Immune checkpoint inhibitors （ICIs） have shown good efficacy in tumor treatment and have changed the landscape of tumor treatment. However， some patients treated with ICIs have not only failed to achieve the desired therapeutic effect， but also developed an atypical response pattern of abnormally accelerated tumor growth， namely hyperprogressive disease （HPD）. The pathogenesis of HPD is still unclear and it is difficult to diagnose， which poses a challenge for clinical identification and treatment decisions. Exploring the underlying mechanism of HPD is important to improve the effect of immunotherapy. Based on the theory of "Yang deficiency and toxic knot"， this paper discussed the mechanism of HPD in immunotherapy from the perspective of "spleen and kidney Yang deficiency and hefty toxic pathogens". It was concluded that the inactivation of p53 oncogene and immunosuppressive microenvironment were the manifestations of the deficiency of healthy qi in the body and declined yang in the spleen and kidney， serving as an important basis for the occurrence of HPD. Adverse reactions caused by ICIs belong to the category of "drug toxicity". The occurrence and development of murine double minute 2 （MDM2）/murine double minute 4 （MDM4） activation， epidermal growth factor receptor （EGFR） mutation， and tumor inflammatory microenvironment are the manifestations of the hyperactivity of pathogenic Qi， conflict of cancer toxicity and drug toxicity， and being hefty by virtue of deficiency， which can promote the abnormal proliferation of tumor cells， and they are the core pathogenic elements of HPD and are closely related to disease prognosis. In terms of treatment， under the guidance of the theory of "five views on differentiation and treatment" （time-space view， core view， symptom view， precision view， and disease-before-onset view）， which was summarized according to the clinical practice of this research team， this paper， taking the prevention and treatment of HPD as the entry point， formulated traditional Chinese medicine （TCM） compounds to reinforce healthy Qi and warm Yang and realize the dynamic management of the whole spatiotemporal cycle， and removed toxins and resisted cancer to realize the all-round systemic intervention of the specimen. Additionally， targets were enriched in the macro-clinical manifestations and microscopic pathological changes of HPD to improve the targeting of drug selection and the precision of prevention and treatment， giving full play to the unique therapeutic advantages of TCM， and providing new ideas for the clinical application of TCM in the prevention and treatment of HPD.
RESUMO
As one of the diseases with high incidence in China， cancer seriously endangers human health. The scientific research and clinical practice of traditional Chinese medicine （TCM） in the prevention and treatment of tumors during the Sixth Five-Year Plan period and the 13th Five-Year Plan period show that TCM has certain advantages in preventing and treating postoperative metastasis and recurrence， prolonging survival period， alleviating adverse reactions， and improving the quality of life of patients with advanced tumors. However， innovation of the TCM theoretical thinking and realization of the TCM full-cycle management are needed urgently， which limits the improvement of clinical efficacy. Malignant tumor is a truly representative of major difficult diseases. The simple mode of syndrome differentiation and treatment cannot meet the clinical needs， and thus the triple mode of disease， syndrome and symptom differentiation and treatment emerged， and has received widespread attention. However， since malignant tumors have their own characteristics of occurrence， development and evolvement， it is urgent to establish a new system of TCM differentiation and treatment for special diseases to adapt to the law of modern disease development. Therefore， on the basis of the triple mode， this paper innovatively proposed a new system of cancer prevention and treatment based on five views on differentiation and treatment in TCM， forming a new paradigm of whole-cycle， whole-chain and all-directional integrated Chinese and western medicine prevention and treatment of tumors. Specifically， time-space view： On the basis of the holistic concept and combined with the complex characteristics of different pathological types， lesion location， disease course and treatment stages of malignant tumors， the dynamic and systematic participation of TCM in the whole process of tumor treatment was brought into play from the time and space dimensions. Core view： The core pathogenesis was summarized based on the combination of disease and syndrome， and its key role in guiding differentiation and treatment of malignant tumors was emphasized. Additionally， the pathogenesis characteristics and evolvement rules of various cancer types in different stages were paid attention. Symptom view： The symptoms were ameliorated and the quality of life was improved. The current obvious contradictions of patients were solved to enhance the humanistic nature of treatment. Precision view： In combination of modern medical concepts， TCM constitutions and laboratory indicators， TCM advantages were enriched and emphasized for precise clinical positioning. Disease-before-onset view： As prevention is more important than treatment， precaution was focused on in each stage of tumors. The five views had different emphases and were interrelated， covering new understandings of the existing TCM prevention and treatment system of malignant tumors. In addition， new ideas and concepts have been introduced on the basis of the original TCM theory， which provided new strategies for the comprehensive prevention and treatment of tumors.
