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ORIGINAL ARTICLE
Year : 2023 | Volume
: 9
| Issue : 3 | Page : 297-306
Lung cancer treatment in traditional chinese medicine: History, current status, and development
Chu-Chu Zhang1, Su-Ying Liu2, Jie Liu2, Pei-Ying Yang3, Hong-Sheng Lin2, Ying Zhang2
1 R & D Department of Special Collection Resources, Institute of Information on Traditional China Medicine, China Academy of Chinese Medical Sciences, Beijing, China
2 Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
3 University of Texas MD Anderson Cancer Center, Houston, TX, USA
Correspondence Address:
Dr. Hong-Sheng Lin
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053
China
Dr. Ying Zhang
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053
China
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/2311-8571.382025
Objective: This article discusses the following aspects, including the history of traditional Chinese medicine (TCM) in the treatment of lung cancer, the breakthrough in the theory of TCM in treatment of lung cancer, clinical study of TCM in treating lung cancer, microscientific interpretation of TCM treatment for lung cancer and the prospect of TCM in treating lung cancer. Materials and Methods: In this paper, through a systematic search, combing traditional Chinese medicine prevention and treatment of lung cancer ancient books and modern literature. Results: A series of large sample and multi-centered clinical studies have proved that TCM comprehensive treatment significantly improves the clinical efficacy for lung cancer. “TCM treatment system for non-small cell lung cancer” based on staged and standardized integration of TCM and Western medicine has been well developed and popularized in practice. Furthermore, in virtue of the international cooperation platform established by the National Cancer Institute of the United States, the scientific connotation of TCM in the prevention and treatment of lung cancer is systematically and deeply studied, thereby promoting the research and development of new Chinese drugs for lung cancer. Conclusions: Nowadays, TCM has realized a landmark breakthrough in treating lung cancer, bringing benefits to all lung cancer patients.
Keywords: Clinical study, lung cancer, mechanism, non-small cell lung cancer, traditional Chinese medicine
The National Cancer Institute (NCI) has recently released the latest Cancer statistics, 2023 on CA. The report revealed that the rate of decline in lung cancer cases among women was half that of men (1.1% vs. 2.6% annually) from 2015 to 2019. This discrepancy can be attributed to the years of dedicated efforts by scholars in clinical and basic research, as well as advancements in early screening, targeted therapy, and immunotherapy specifically applied to lung cancer treatment.[1] In the field of traditional Chinese medicine (TCM), various treatment approaches have been advocated, including protective therapy, loading therapy, consolidation therapy, maintenance therapy, and simple TCM therapy, all based on evidence-based medicine for the treatment of lung cancer.[2],[3],[4],[5] These approaches have benefits for lung cancer patients in terms of preventing lesion enlargement, improving symptoms and overall quality of life, and prolonging survival.[6],[7],[8],[9],[10]
The History of Traditional Chinese Medicine in the Treatment of Lung CancerIn ancient times, physicians classified lung cancer into categories known as Feiji or Xiben (the accumulation of the lung). Feiji was first recorded in the book Classic of Questioning, stating that “Feiji, also called Xiben, is located in the right hypochondriac region and can grow as large as a cup. If left untreated for a prolonged period, patients may experience symptoms such as chills, fever, asthma, and cough, thereby inducing lung abscess.” These symptoms, such as cough, chest pain, and hemoptysis are similar to those commonly associated with lung cancer. Miraculous Pivot recorded that “patients exhibit signs of weak bones, emaciated muscles, chest fullness, and wheezing,” symptoms that also resemble those seen in advanced stages of lung cancer and the clinical manifestations of malignancy in a qi-exhausted stage. Pulse Classics by Wang Shuhe in the Western Jin Dynasty described that “patients with Feiji usually present symptoms of reversed flow of qi under the hypochondrium, dragging pain in the back, and a floating and superficial pulse,” similar to the symptoms of advanced lung cancer, as well as axillary and supraclavicular lymph node enlargement induced by hepatic and lymphatic metastases or subcutaneous metastasis.
During the Jin and Yuan Dynasties, Liu Wansu greatly influenced future physicians by advocating the use of heat-clearing and detoxifying methods in the treatment of lung cancer. Zhu Danxi expressed the belief that “If healthy qi is nourished, accumulation is spontaneously removed.” In the Ming and Qing Dynasties, Zhang Jingyue emphasized the need for flexible and adaptive therapies based on the varying conditions of patients' constitution, the deficiency or excess of the viscera, and the progression of the disease. Ye Tianshi demonstrated expertise in the use of insect-based drugs during treatment. Wang Qingren believed that promoting blood circulation and removing blood stasis was an effective approach to treatment. Together, these diverse treatment concepts form a comprehensive theoretical system for the treatment of lung cancer, as found in ancient TCM books [Figure 1].
Since the 1970s, TCM oncologists from previous generations, such as Yu Guiqing and Piao Bingkui,[11] have conducted a series of studies based on the theory of “strengthening vital qi and consolidating body resistance.” These studies have verified that drugs with the ability to strengthen vital qi can improve patients' physical condition. As research into TCM treatment for this disease continues to deepen, an increasing number of new theories, treatment strategies, and drugs are emerging.
Yu Rencun[12] suggests that selecting methods to supplement qi and consolidate the root, promote blood circulation, and remove blood stasis is appropriate for treating adverse reactions induced by radiotherapy and chemotherapy in the treatment of lung cancer. Liu Jiaxiang[13] argues that TCM physicians should apply treatment principles of disease differentiation and syndrome differentiation, focusing on strengthening the body's resistance and combining it with anticancer measures based on overall and local patient manifestations. In addition, he emphasizes the importance of a flexible selection of yang-warming drugs. Professor Zhou Daihan[14] insists on the treatment method of “harmonizing by warm-natured medicine,” emphasizing the removal of both qi and phlegm. Professor Zhou Zhongying[15] believes that the main pathogenesis of lung cancer involves phlegm stagnation, blood stasis in the lung, and depletion of qi and yin due to toxicity, with the former being the major pathological factor. The disease initially manifests in the lung and progresses to affect the five viscera at later stages.
The Breakthrough in the Theory of Traditional Chinese Medicine in Lung Cancer TreatmentExtensive studies on the etiology and pathogenesis of lung cancer have revealed that although TCM exhibits lower cytotoxicity towards lung cancer tumor cells, it inhibits the formation of tumors rather than directly killing tumor cells. Thus, it is believed that the concept of “strengthening vital qi and nourishing the root” alone fails to fully encompass the advantages and characteristics of TCM in the treatment of malignant tumors.
Professor Lin Hongsheng[16],[17],[18],[19],[20] found that adhering strictly to the theory of “strengthening vital qi and consolidating body resistance” poses challenges in achieving the goal of prolonging survival time for patients with highly malignant lung cancer. Conversely, administering anti-tumor drugs with functions such as phlegm elimination, mass resolution, toxicity removal, and heat-clearing, tailored to patients' physical conditions, can provide adequate time to strengthen healthy qi and achieve equilibrium between yin and yang. Therefore, she proposes that the theory of “consolidating body resistance and eliminating the source” aligns better with the characteristics of TCM in treating malignancies.
“Consolidating body resistance and eliminating the source” emphasizes the protection of the body's “healthy qi” during TCM treatment, thereby improving the immune microenvironment. In addition, TCM therapies rooted in this theory aim to eliminate the pathogenic factors of lung cancer, preventing the development of tumor “toxicity.” Thus, TCM physicians should adopt a comprehensive approach encompassing both offensive and defensive strategies based on the underlying pathogenesis while incorporating the principles of “consolidating body resistance” and “eliminating the source.” In these studies, Professor Lin Hongsheng emphasized the theory of seed and soil, which focuses on the suppression of tumor cells and the improvement of overall immune function. These studies have been confirmed through nearly two decades of collaboration with the National Cancer Center. The theory of “consolidating the resistance and eliminating the source,” which is widely accepted and applied in modern Chinese medicine, plays a major role in the provision of personalized and precise therapies for the treatment of lung cancer [Figure 2].
Clinical Status of Traditional Chinese Medicine in Treating Lung CancerGuided by the principle of “consolidating the root and eliminating the source,” the TCM treatment of non-small cell lung cancer (NSCLC) categorizes TCM treatment into five stages: Protective therapy, consolidation therapy, maintenance therapy, loading therapy, and TCM syndrome differentiation therapy, collectively referred to as the “five treatments.” Through full-cycle management, TCM treatment for lung cancer enhances effectiveness and reduces toxicity in various areas, including postoperative therapy, chemoradiotherapy, targeted therapy, immunotherapy, late maintenance therapy, and rehabilitation.
Application of traditional Chinese medicine in perioperative lung cancer treatment
Surgical resection is the preferred treatment option for lung cancer. The theory of TCM holds that radical surgery focusing on the removal of tumor cells can easily harm the qi and blood, leading to internal deficiencies. In contrast, TCM is conducive to creating favorable conditions for patients undergoing surgery by regulating yin and yang, tonifying qi and blood, promoting postoperative recovery, preventing postoperative recurrence, and reducing distant metastasis.
Wang et al. conducted a multicenter prospective cohort study to investigate the application of TCM in patients with NSCLC.[21] They found that high exposure to TCM was associated with better DFS. In a subgroup exploratory analysis, TCM therapy was identified as a protective factor against cancer recurrence and metastasis in NSCLC patients post-surgery, with even longer DFS observed in patients treated with TCM. Su et al. recruited patients (TCM intervention group) who underwent NSCLC surgery.[22] They used modified Shengjiang Decoction as the primary formula based on syndrome differentiation. The results showed significant improvements in item scores, including shortness of breath, cough, expectoration, chest tightness, fatigue, susceptibility to cold, loss of appetite, and insomnia compared to the pretreatment scores (P < 0.05 or P < 0.01).
Application of traditional Chinese medicine in chemotherapy for lung cancer
TCM holds an important position in reducing tumor burden and prolonging the survival time of lung cancer patients. Overall, TCM focuses on supplementing qi and blood while regulating yin and yang. This approach not only improves the quality of life for patients but also plays a vital role in enhancing the effectiveness of radiotherapy and chemotherapy, as well as inhibiting recurrence and metastasis.
Zheng conducted a multicenter prospective randomized controlled trial involving patients with advanced NSCLC.[23] The treatment group followed a standardized treatment based on the NCCN guidelines, combined with a comprehensive program that aimed to invigorate the spleen and stomach, nourish qi and blood, and nourish the liver and kidney. In contrast, the control group received only a single treatment based on NCCN guidelines. The results indicated significant differences between the treatment group and the control group in terms of clinical symptoms such as fatigue, loss of appetite, nausea, and vomiting (P < 0.05). Chen et al. discussed the effects of supplementing Sijunzi Decoction in lung cancer patients with qi and yin deficiency syndrome who experienced chemotherapy-related myelosuppression.[24] The control group received the standard chemotherapy regimen (TP), while the observation group was administered supplemented Sijunzi Decoction in addition to the control group treatment. The results revealed that the observation group showed an increase in the number of neutrophils, hemoglobin, platelets, and white blood cells, as well as a lower TCM symptom score compared to the control group (P < 0.01). Ren et al. used the Xuanfu Daizhe Decoction to treat Chemotherapy-induced nausea and vomiting in lung cancer patients.[25] The control group received conventional Western medicine for antiemesis, while the observation group received Xuanfu Daizhe Decoction as well as the control group treatment. The efficiency of Xuanfu Daizhe Decoction in controlling nausea and vomiting was superior to that of the control group.
Application of traditional Chinese medicine in radiotherapy for lung cancer
Exposure to radiation can easily lead to a deficiency of qi and yin in the body. According to TCM, radiation falls under the categories of “heat evil,” “heat toxin,” or “fire evil.” When heat toxin invades the body, it often results in an internal excess of heat toxin and impairment of Jin fluid. The lungs are tender organs and are unable to endure extreme cold and heat; therefore, lung cancer patients undergoing radiotherapy are more susceptible to manifestations of consumption of lung yin and qi. Radiotherapy can easily trigger adverse reactions, including fatigue, loss of appetite, low fever, suppression of hematopoietic function in the bone marrow, radiation pneumonia, and pulmonary fibrosis, cavity formation caused by cancer necrosis and liquefaction, local skin injury, and other complications.
“Erhuang Decoction” spray (composed of Huanglian, Huangbai, and Huzhang) is a cost-effective and user-friendly treatment option. A large-scale and multi-center randomized controlled clinical trial has demonstrated its remarkable efficiency in relieving pain in radiated skin and alleviating related symptoms (including erythema, skin peeling, and edema) of local skin injury.[26] Furthermore, this decoction has shown promising effects on wound healing, TCM clinical symptoms, KPS score, and quality of life score among patients with malignant tumors suffering from radioactive skin injuries.
Application of traditional Chinese medicine in targeted therapy
Targeted therapy is a cellular and molecular-level treatment that involves binding specifically designed drugs to definite oncogenic sites, resulting in the programmed death of tumor cells while leaving normal cells unaffected. At present, targeted therapy for NSCLC can be classified into the following categories: estimated glomerular filtration rate- tyrosine kinase inhibitors (EGFR-TKIs), anaplastic lymphoma kinase inhibitors, and vascular endothelial growth factor (VEGF) inhibitors. However, this approach has disadvantages such as the development of drug resistance and varying degrees of damage to the skin and cardiovascular system due to long-term use. To overcome these challenges, TCM treatment combined with targeted therapy offers several advantages, including enhanced efficacy, reduced toxicity, and the potential to reverse drug resistance to targeted drugs.
Wang et al. conducted a study to evaluate the efficacy of self-designed Rash Particles (Chishao, Shihu, Baixianpi, Fangfeng, Jinyinhua) in the treatment of EGFR-TKI-related rash.[27] A total of 104 patients who developed rashes after oral administration of EGFR-TKI were randomly assigned to either the treatment group or the control group. The treatment group was given self-designed Rash Particles for oral administration, while the control group received a topical silicone oil emulsion. Both groups experienced an improvement in their skin rash, but the treatment group showed greater improvement and faster remission of the rash compared to the control group (P < 0.05). In another prospective randomized controlled study, Shi recruited 70 patients with NSCLC who experienced diarrhea after receiving targeted drugs.[28] The experimental group was treated with TCM Diarrhea Prescription (Huangqi, Qianshi, Qinpi, and Zhike), while the control group was treated with imontarum. By the 14th day, the diarrhea remission rates of the control group and the experimental group reached 76.67% and 81.82%, respectively, indicating a significant difference between the two groups (P = 0.029).
Application of traditional Chinese medicine in immunotherapy
NSCLC has entered the era of immunotherapy with the widespread use of monoclonal antibody programmed cell death protein-1 (PD-1), such as pembrolizumab, nabuliumab, and camrelizumab, in clinical practice. Although the 5-year survival rate of patients significantly improved,[29] various adverse reactions, such as rash, fatigue, immune hypothyroidism, hyperthyroidism, myocarditis, pneumonia, and hepatitis, are frequently observed during or after treatment. The combination of TCM therapy and immunotherapy improves the aggregation of immune effector cells in NSCLC patients, enhances the depletion of immune cells and bypass activation after immunotherapy, and delays the onset of drug resistance, thereby playing a key role in reducing toxicity and enhancing efficacy.[30]
In a study conducted by Chen,[31] patients with advanced lung cancer were recruited and treated with orally administered Chinese herbs known for replenishing qi and removing phlegm, in combination with PD1/PD-L1 therapy. Out of the 84 cases, disease progression was observed in 55 cases, while the remaining 29 cases showed improvement, with a median optimal therapeutic duration of 9.4 months. A total of 36 patients experienced optimized curative effects and 48 patients were considered as truncated data, with a median optimal curative duration of 9.4 months. Moreover, 63 patients discontinued immunotherapy and 21 were considered truncated data, with a median duration of immunotherapy of 9.2 months. Thus, the oral administration of Chinese herbs with qi-replenishing and phlegm-removing functions, in combination with PD1/PD-L1 therapy, demonstrated more ideal therapeutic efficacy and improved survival outcomes.
Application of traditional Chinese medicine maintenance therapy in advanced lung cancer
TCM maintenance therapy enables us to achieve the following objectives: Relieving symptoms, improving quality of life, increasing disease control rate, and prolonging survival. Compared to chemotherapy and targeted therapy, TCM maintenance therapy demonstrates fewer adverse reactions, greater safety and compliance, and a lower economic impact. Therefore, it is recommended as a preferred choice for treating advanced NSCLC.
Liu et al. reported on the efficacy of Feitai Capsule, which consists of Huangqi, Xianhecao, Tiannanxing, Banzhilian, and other ingredients, in advanced NSCLC patients.[32] The results showed that the median progression-free survival of the experimental group and the observation group were 6.23 months and 4.67 months, respectively (P = 0.048). Shao and Chen randomly divided 100 NSCLC patients with stable disease conditions, who responded well to chemotherapy in stages IIIb to IV, into an observation group (taking Compound Banmao Capsules) and a control group (taking a placebo with supportive treatment) to observe the effect of Compound Banmao Capsules.[33] The results demonstrated that the observation group had a higher effective rate than the control group (56% vs. 38%, P < 0.01). The 2- and 3-year survival rates of the observation group were 22.24% and 13.45%, respectively, which were higher compared to 19.65% and 9.53% of the control group (P < 0.01).
Application of traditional Chinese medicine in rehabilitation of lung cancer
During the rehabilitative period, most patients are prone to various problems, such as psychological disorders, dysfunction, nutritional disorders, physical disabilities, and obstacles to reintegrating into society.
Wang et al. conducted a multicenter, large-sample cohort study. The observation group was treated with a comprehensive treatment plan, including herbal decoction based on syndrome differentiation, exercise and psychological care, diet and functional care, and paste formula.[34] The results showed significant improvements in their anxiety and depression. Furthermore, the study aimed to explore the efficacy of a tonic paste formula known for being “gentle in nature and specific in efficacy.” Patients in the treatment group were orally administered Yifei Qinghua Paste on the basis of conventional Western medicine treatment.[35] The treatment group exhibited significant changes in KPS score, body weight, and immune function compared to the control group (P < 0.05 or P < 0.01).
According to TCM, the concept of the “five treatments and five nourishments” is based on the principles of mutual rooting and interdependence. The purpose of the “five nourishments” is to strengthen patients' constitution, thereby creating favorable physical conditions for the “five treatments.” This approach is beneficial in enhancing patients' endurance during treatment and accelerating the rehabilitation process. The “five nourishments” in TCM encompass psychological cultivation, exercise cultivation, diet cultivation, function cultivation, and paste cultivation. By incorporating these aspects into the entire course of rehabilitative treatment, with the principles of the “five nourishments” and “five treatments” for lung cancer, the overall quality of life can be improved, and the prognosis can be enhanced [Figure 3].
Figure 3: Clinical status of traditional Chinese medicine in treating lung cancer Microscientific Interpretation of Traditional Chinese Medicine Treatment for Lung Cancer With the constant advancement of modern medicine, TCM, guided by evidence-based, individualized, and standardized approaches, also endeavors to establish a comprehensive evaluation system for the efficacy of lung cancer treatment. The progress made in immunology, genetics, molecular biology, and other fundamental disciplines have opened up possibilities for in-depth research at the cellular, molecular, and genetic levels. TCM therapies have the ability to regulate immune function, as well as adjust biological processes such as cell differentiation, proliferation, adhesion, morphogenesis, and phenotypic expression, thereby improving the inflammatory environment and hindering the progression from inflammation to cancer. Moreover, they can impede tumor cell proliferation, induce tumor cell apoptosis, inhibit tumor angiogenesis, and promote autophagy through comprehensive regulation of multiple channels and targets [Figure 4].
Figure 4: The mechanism of traditional Chinese medicine treatment of lung cancerImprovement of the body's immunity
The occurrence and progression of lung cancer are closely correlated with a decline in immune surveillance against tumors. TCM is able to boost immunity by strengthening the healthy qi, thereby achieving anticancer effects through an increase in the number or function of tumor-killer cells.
The main component of cinobufotalin is a refined liposoluble substance extracted from dried toad skin using scientific methods.[36],[37],[38],[39] Cinobufagin, which is the bioactive compound found in cinobufotalin, has been proven to have strong anticancer effects. Patients who underwent chemotherapy in combination with cinobufotalin showed a higher proportion of Th17 cells and a lower proportion of Treg cells compared to the control group. This suggests that cinobufotalin has the ability to upregulate interleukin (IL)-17 and downregulate tumor growth factor-β, thereby promoting the anti-tumor function and reducing the tumor immunosuppressive effects of tumors. Zhang et al. discovered that mice with Lewis lung carcinoma had significantly higher levels of IL-10 in their spleens compared to IL-2, resulting in a Th1/Th2 drift.[40] Qiyu Sanlong Decoction (Huangqi, Yuzhu, Tianlong, Dilong, Longkui, Baihua Sheshecao, Yiyiren, Zexi, Ezhu, Chuanbei) could significantly improve the level of Th1 cells. Fang et al. found that mice with Lewis lung cancer tumors had lower spleen lymphocytes proliferation and an increased ratio of CD4+CD25+Treg cells compared to normal mice.[41] Jianpi Jiedu Formula (Shenghuangqi, Dangshen, Fuling, Gancao, Maidong, Shudi, Xianlingpi, Qiyeyizhihua, and honeycomb) exerts its anti-tumor effects by increasing the proliferation of spleen lymphocytes, reducing the ratio of CD4+CD25+Treg cells, and inhibiting tumor growth to some extent in mice.
Inhibition of tumor cell proliferation
Uncontrollable activation of the cell cycle is a characteristic feature of cell hyperproliferation in cancer cells. Following the M phase, cancer cells either reenter the G1 phase or temporarily arrest in the G0 phase. Chinese drugs have the ability to interfere with the cell cycle of tumor cells, thus inhibiting tumor growth.
Liang et al. conducted a study to investigate the effects of a Chinese herbal formula utilizing flow cytometry and Reverse transcription polymerase chain reaction.[42] They observed that Tiaoqi Xiaoji Decoction (Chaihu, Huangqin, Renshen, Banxia, Zhigancao, Shengjiang, Dazao, Tiandong, Shengmuli, Ezhu, Baihua Sheshe Cao) could block the transition from the S phase to the G2/M phase, reduce the proportion of cells in the mitotic phase, and inhibit cell proliferation. Vermenin capsules were found to inhibit the growth of cancer cells, arresting them in the G0 to G1 phases, thus preventing them from entering the S phase for DNA replication and ultimately inhibiting tumor growth.[43]
Induction of tumor cell apoptosis
Cell apoptosis is a physiological process strictly regulated by multiple genes, including Caspase family, Bcl-2 family, and the tumor suppressor gene P53.
It has been reported that platycodon D exhibits the ability to induce apoptosis in lung cancer by regulating the JNK/PUMA pathway.[44],[45],[46],[47] Elemene has been shown to reduce the division of lung cancer A549 cells, impeding their growth in the S phase and facilitating their apoptosis.[48],[49],[50],[51],[52] Furthermore, some Chinese drugs can induce tumor cell apoptosis by modulating the expression of certain proteins in lung cancer. For instance, Baihua Sheshe Cao (Hedyotis Diffusae Herba) injection has been found to induce apoptosis in human lung cancer SPC-A-1 cells, likely through the upregulation of P53 protein expression and the downregulation of Bcl-2 and NF-k B protein expression.[53],[54],[55]
Inhibition of tumor angiogenesis
The increased expression of angiogenic factors in tumors is one of the causes of abnormal hyperplasia of blood vessels in tumor tissue. Therefore, an important approach to tumor treatment is to inhibit tumor angiogenesis by suppressing VEGF.
Kangaike Injection demonstrates anti-tumor effects by inhibiting angiogenesis, invasion, and metastasis, as well as reducing VEGF levels in advanced NSCLC patients, thereby improving their prognosis.[56] Chen et al. compared the effects of four groups of commonly used Chinese medicines with the ability to supplement qi and strengthen the body's resistance (Shenghuanqi, Nvzhenzi), dispel phlegm and eliminate stagnation (Banxia, Tiannanxing), promote blood circulation and remove blood stasis (Ezhu, Yujin), and clear heat and detoxify (Baihua Sheshe Cao, Banzhilian) against Lewis lung cancer and their mechanisms.[57] All four groups of anti-cancer medicines were found to inhibit tumor angiogenesis by inhibiting VEGF and MMP-2, with the detoxifying group showing the strongest suppression of VEGF expression. The combined group exhibited remarkable advantages in reducing MMP-2 expression levels and improving the expression of ES.
Autophagy
One of the main mechanisms of TCM's anti-tumor action is its regulation of the autophagy process. Autophagy, a process of cellular self-degradation, plays essential homeostatic roles. However, continuous and excessive autophagy inhibits tumor development.[58]
Honokiol can induce autophagy and apoptosis of tumor cells by regulating the AMPK-m TOR signaling pathway.[59],[60],[61],[62],[63] Psoralen has the ability to induce autophagy and inhibit the proliferation of A549 cells by generating reactive oxygen species.[64],[65] Matrine has gained attention in recent years. LC3-II, which is located on the surface of preautophagic vesicles and autophagic vesicles, serves as a specific marker of autophagy vesicles. The use of native compounds of matrine significantly increases the levels of LC3-II protein, thereby inducing autophagy in lung cancer A549 cells [Table 1].[66],[67],[68],[69],[70]
Table 1: The mechanism of traditional Chinese medicine treatment of lung cancer Prospect of Traditional Chinese Medicine in Treating Lung Cancer An increasing number of studies has been put forward regarding the theory of TCM in the prevention and treatment of lung cancer.
Li Jie discussed the occurrence, development, and metastasis of tumors using the concept of “yin and yang.”[71] Guided by the theory of “yang transforming qi and yin forming the shape,” it is appropriate to distinguish the waxing and waning of yin and yang in the body and the tumor, dissipating the yin and inhibiting the yang of the tumor. Cheng Haibo proposes three key points of pathogenesis differentiation for cancer toxin.[72] First, it is important to distinguish the pathogenic characteristics of cancer toxin. Second, differentiation of nonspecific pathogenic factors, including depression, wind, cold, heat, dampness, phlegm, and blood stasis is necessary. Finally, he suggests that the basic pathogenesis of malignancy is “the accumulation of evil toxin and deficiency of healthy qi.” Hua Baojin proposes the concept of regulating qi and detoxifying cancer to prevent and treat cancer.[73] He considers that the core pathogenesis of cancer is the disorder of qi activity and the internal accumulation of toxins, and that clinical treatments should follow the principles of syndrome differentiation and disease differentiation in combination.
In terms of clinical practice in the prevention and treatment of lung cancer using TCM, relevant experts, and scholars in this field across China have organized to formulate the Guidelines for TCM Diagnosis and Treatment of Malignant Tumors.[74] These guidelines include a mature, principled, and standardized system for TCM diagnosis and treatment in current clinical practice, along with recommendations for physicians based on international standards for grading evidence in evidence-based medicine.
In 2021, the China Association of Integrated Traditional and Western Medicine released Expert Consensus on the Diagnosis and Treatment of Lung Cancer by Integrated Traditional Chinese and Western Medicine. In recent years, a series of high-level evidence-based medical studies have been conducted on TCM treatment for lung cancer, proving its unique advantages in reducing the toxic and side effects caused by radiotherapy and chemotherapy, relieving clinical symptoms, and enhancing the quality of life. We anticipate the emergence of more large-scale, multi-centered, and high-quality clinical studies on international platforms to establish TCM treatment as an international consensus in this field. Furthermore, the establishment of an internationally recognized evaluation system for the efficacy of TCM in the prevention and treatment of lung cancer is crucial.
In terms of the basic research on the prevention and treatment of lung cancer using TCM, the development of network pharmacology, bioinformatics, and artificial intelligence provides opportunities to elucidate the essence and scope of TCM theory in lung cancer prevention and treatment. This advancement also enables the exploration of the underlying micro-mechanisms of the “inflammation-cancer transformation” chain.[75],[76],[77],[78],[79] By screening large biological samples and studying multiple pathways and targets, we can identify common biological characteristics in the dominant population and regulate the signaling pathway of lung cancer. This contributes to further improvements in the efficacy of TCM in preventing and treating lung cancer.[80],[81],[82],[83],[84]
Moreover, conducting in-depth studies on genomics, proteomics, and metabolomics allows us to observe changes in the type, quantity, and spatial structure of proteins during tumor occurrence and development. These comprehensive, dynamic, and quantitative approaches will also help regulate the homeostasis of the internal environment and differential metabolites. Such studies not only help in revealing the pathogenesis of malignant tumors but also assist in identifying tumor markers for early clinical diagnosis and new therapeutic targets.
ConclusionThrough the dedicated efforts of Chinese physicians across four generations, TCM has made remarkable progress in the field of lung cancer prevention and treatment over the course of 30 years. A series of large-scale, multi-centered clinical studies have demonstrated that TCM comprehensive treatment greatly improves the clinical efficacy of lung cancer treatments. The TCM treatment system for NSCLC, which is based on the staged and standardized integration of TCM and Western medicine, has been well-developed and widely adopted in practice. Before this, no systematic approach for the prevention and treatment of lung cancer had been established as a treatment guideline. Furthermore, through the international cooperation platform established by the NCI of the United States, the scientific connotation of TCM in the prevention and treatment of lung cancer has been systematically and comprehensively studied, thereby promoting the research and development of new Chinese drugs for lung cancer. In addition, TCM, guided by the principles of cultural inheritance and innovation, has gained public recognition and international awareness. Nowadays, TCM is undergoing a process of modernization and has evolved into an evidence-based therapy rather than merely an alternative medicine. It has achieved a major breakthrough in the treatment of lung cancer, benefiting patients with this condition worldwide.
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The authors all consent to the publication of this paper.
Availability of data and materials
All data and materials generated and analyzed during the present study are available from the corresponding author on reasonable request.
Authors' contributions
Chu-Chu Zhang designed the study. Jie Liu performed the review. Hong-Shen Lin provided research guidance. Pei-Ying Yang conducted data analysis. Ying Zhang and Su-Ying Liu contributed to writing assistance and proofreading the manuscript. All authors contributed to the article and approved the submitted version.
Financial support and sponsorship
This work was supported by the Fundamental Research Funds for the Central public welfare research institutes (No. 2020YJSZX-3).
Conflicts of interest
There are no conflicts of interest.
References
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