Traditional Chinese Medicine in Gastric Cancer: A Narrative Review of Mechanisms, Clinical Evidence, Technical Advances, and Translational Challenges

Abstract

Gastric cancer remains one of the most common malignant tumors worldwide and is associated with a high disease burden. Its treatment is still challenged by multidrug resistance, an immunosuppressive tumor microenvironment, and suboptimal postoperative recovery. Traditional Chinese Medicine (TCM) has shown potential in the prevention, treatment, and rehabilitation of gastric cancer. Herein, this review aims to discuss the basic theory, clinical practice, technical progress, epidemiological research, controversies and challenges, and future prospects of TCM in gastric cancer treatment. Literature from the past five years was retrieved from PubMed and China National Knowledge Infrastructure (CNKI) using English and Chinese search terms related to gastric cancer, TCM, Chinese herbal medicine, integrated traditional Chinese and Western medicine, clinical outcomes, mechanisms, network pharmacology, metabolomics, immunotherapy, chemotherapy resistance, postoperative recovery, and translational research. Experimental studies, clinical studies, cohort studies, randomized trials, meta-analyses, guideline-related studies, and technical studies were considered only if they were relevant to the scope of this narrative review. Based on these, we discuss how TCM may exert potential anti-gastric cancer effects through the regulation of apoptotic pathways, modulation of signaling networks, and improvement of immune function. Currently, clinical studies indicate that TCM combined with chemotherapy may prolong survival in patients with advanced gastric cancer, while perioperative interventions such as transcutaneous electrical acupoint stimulation and herbal formulations may alleviate postoperative pain, promote gastrointestinal recovery, and regulate inflammatory responses. Technological advances such as network pharmacology, metabolomics, and nano-preparation technologies have been used to help clarify the molecular mechanisms of TCM and improve drug delivery efficiency. In addition, observational and real-world evidence suggest that TCM use is associated with survival-related outcomes, patient acceptance, and regional differences in clinical application patterns. Despite these findings, challenges remain, including insufficient high-quality clinical evidence, lack of standardization in syndrome differentiation and efficacy evaluation, and the need for more rigorous safety assessment. Overall, TCM may serve as a complementary component of integrated gastric cancer management, particularly in supportive care, postoperative recovery, and treatment tolerance, but its clinical value remains dependent on the quality of supporting evidence. Future studies should use standardized protocols, rigorous clinical designs, reproducible quality-control systems, and appropriate safety assessment to define its role within modern precision oncology.

Introduction

Gastric cancer is one of the most common malignant tumors worldwide and remains associated with a high disease burden, while its treatment is still challenged by multidrug resistance, an immunosuppressive tumor microenvironment, and suboptimal postoperative recovery.^1,2 Traditional Chinese Medicine (TCM) has increasingly been explored as a complementary component of comprehensive gastric cancer management because of its potential roles in overall regulation, multi-target intervention, treatment tolerance, and postoperative rehabilitation.^3,4 Its therapeutic framework emphasizes strengthening body resistance (ie, supporting the patient’s overall functional reserve, immune status, nutritional condition, and tolerance to treatment) while eliminating pathogenic factors (ie, reducing disease-promoting conditions such as toxin accumulation, phlegm-dampness, blood stasis, or heat-related inflammatory states), thereby regulating qi and blood, and maintaining the balance of yin and yang. In this context, qi and blood are terms describing functional activity, circulation, nourishment, and tissue homeostasis. Through these principles, TCM may exert anti-gastric cancer effects by modulating multiple biological mechanisms, including apoptotic pathways, signaling networks, and immune function. For instance, baicalein has been shown to induce apoptosis in gastric cancer cells,⁴ and the Zuojin Pill can reverse resistance to cisplatin.⁵

From a clinical perspective, the combination of TCM with chemotherapy has been associated with improved survival in patients with advanced gastric cancer, with evidence indicating that those receiving TCM for more than 180 days experienced a 63% reduction in the risk of death.^3,6 Furthermore, during postoperative rehabilitation, interventions such as transcutaneous electrical acupoint stimulation (TEAS) have been shown to alleviate pain and facilitate the recovery of gastrointestinal function,⁷ and formulations such as the Jiawei Pingwei Baohe Decoction contribute to the regulation of inflammatory responses and immune function.⁸

With the ongoing integration of modern technologies, including systems pharmacology and nano-preparation strategies, the molecular targets of TCM have been progressively elucidated, and notable advances have been achieved in both drug development and precision delivery.^9,10 However, important challenges remain, such as rigorous scientific validation, standardization of syndrome differentiation (ie, classifying patients according to patterns of symptoms, tongue and pulse findings, constitution, and disease stage, so that treatment can be individualized rather than based only on tumor type), and the establishment of reliable efficacy evaluation systems.^11,12 In the future, the integration of TCM with immunotherapy, together with personalized treatment approaches guided by molecular diagnostics, is expected to open more precise and targeted therapeutic avenues for gastric cancer management.^13,14

Herein, this narrative review was designed to summarize current evidence on TCM in gastric cancer, including its theoretical basis, pathophysiological interpretation, treatment application, integration with modern medical theory, clinical practice, technical progress, real-world use, controversies, and future prospects. Literature from the past five years was searched in PubMed and China National Knowledge Infrastructure (CNKI), and relevant older studies were also considered when they provided important clinical, mechanistic, or methodological evidence. The literature retrieval process is shown in Supplementary Material S1. Experimental studies, clinical studies, cohort studies, randomized trials, meta-analyses, guideline-related studies, network pharmacology studies, omics-based studies, and technical studies were included when relevant to the scope of this review. To avoid overinterpretation of heterogeneous evidence, the included studies were interpreted according to study type: randomized controlled trials and meta-analyses were regarded as the main sources of clinical evidence, while cohort studies and retrospective studies were interpreted as observational evidence, and cell experiments, animal studies, network pharmacology, molecular docking, metabolomics and drug-delivery studies were considered exploratory evidence requiring further validation.

Pathophysiological Mechanisms of Gastric Cancer

The occurrence and development of gastric cancer is a complex, multistep process involving the interplay of genetic, environmental, microbial, and other contributing factors. Helicobacter pylori (H. pylori) infection remains a well-established risk factor for gastric cancer and contributes to carcinogenesis through mechanisms such as gastric mucosal atrophy and secondary hypergastrinemia. In addition, gastrin exerts trophic effects on the gastric oxyntic mucosa, and sustained hypergastrinemia may further increase the risk of malignant transformation.² At the molecular level, accumulating evidence has highlighted the critical roles of dysregulated cell proliferation, imbalance of apoptosis, and aberrant activation of intracellular signaling pathways in gastric tumorigenesis. For example, Bai et al reported that BJ-13, a novel benzamide derivative, induces the accumulation of reactive oxygen species (ROS) and triggers mitochondrial membrane potential collapse and activation of the apoptotic pathway via the upregulation of Bax, downregulation of Bcl-2, and activation of cleaved Caspase-3.¹⁵

Peritoneal metastasis represents a major determinant of poor prognosis in gastric cancer. Due to the presence of the blood-peritoneal barrier, systemically administered agents often fail to achieve effective concentrations within peritoneal lesions, whereas intraperitoneal administration of paclitaxel (PTX) can enhance drug retention and penetration at these sites.¹⁶ In addition, the immunosuppressive tumor microenvironment plays a pivotal role in disease progression. Myeloid-derived suppressor cells (MDSCs) exert immunosuppressive effects through activation of the PI3K/AKT serine/threonine kinase 1 (AKT1)/mechanistic target of rapamycin (mTOR)-dependent glycolytic pathway, while Eleutheroside A, an active component of Acanthopanax senticosus, has been shown to attenuate the immunosuppressive capacity of MDSCs by inhibiting this pathway, thereby suppressing gastric cancer growth.¹ This multifactorial nature provides a strong mechanistic foundation for therapeutic strategies that target multiple pathways simultaneously, which is consistent with the holistic and multi-target characteristics of TCM.

From the perspective of TCM, the pathophysiology of gastric cancer is understood as a dynamic and progressive process involving both deficiency of vital qi and accumulation of pathogenic factors. The spleen and stomach are regarded as the main organs responsible for digestion and transformation, and dysfunction in these organs is therefore considered the fundamental basis for disease development.¹⁷ Long-term impairment of spleen-stomach function may lead to insufficient transformation of nutrients and internal weakness, which creates a favorable internal environment for disease progression.¹⁸ On this basis, the development of gastric cancer is often attributed to a combination of deficiency and excess patterns.¹⁹ Deficiency of spleen and stomach qi, or combined qi and yin deficiency, may reduce the body’s ability to maintain normal physiological balance, while pathogenic factors such as dampness, phlegm, heat, and blood stasis gradually accumulate.¹⁹ These pathological factors can obstruct the normal circulation of qi and blood within the digestive system, leading to local stagnation and, over time, the formation of masses. In this context, the interaction between deficiency and excess is considered central to the pathogenesis of gastric cancer.

In addition, emotional factors, dietary habits, and external pathogenic influences are also regarded as important contributors. For instance, improper diet habits, such as excessive intake of greasy, spicy or irregular meals, may damage spleen-stomach function and promote the formation of dampness and heat.²⁰ Emotional disturbances may lead to liver qi stagnation, which in turn affects the normal function of the spleen and stomach, further aggravating qi stagnation and blood stasis.²¹ These factors interact over time and contribute to the progression from functional disorder to structural lesions. At different stages of disease, the dominant TCM syndromes may vary. In the early stage, spleen-stomach deficiency or dampness accumulation may predominate,²² whereas in more advanced stages, patterns such as blood stasis, toxin accumulation and combined deficiency-excess syndromes may become more evident.²³ This staged evolution reflects the dynamic nature of TCM pathophysiology and provides the theoretical basis for syndrome differentiation and individualized treatment. Importantly, these traditional concepts can be partially interpreted alongside modern biomedical observations, although they should not be regarded as direct one-to-one equivalents. For example, “qi deficiency” may correspond to impaired metabolic and immune function,²⁴ and “blood stasis” may correspond to microcirculatory disturbance and a hypoxic tumor microenvironment.²⁵ Similarly, the “phlegm-dampness” and “heat toxin” may relate to chronic inflammation, metabolic dysregulation and accumulation of pro-tumorigenic factors. Although these correlations are still under investigation, they offer a framework for integrating TCM theory with contemporary pathophysiological insights.

Overall, TCM conceptualizes gastric cancer as a progressive process driven by the interaction between deficiency of vital functions and accumulation of pathogenic factors, and this framework provides a complementary perspective that may help explain disease development and support individualized treatment strategies when integrated with modern biomedical understanding.

Application of TCM in the Treatment of Gastric Cancer

The application of TCM in gastric cancer treatment is based on the principles of syndrome differentiation and overall regulation, with therapeutic strategies aimed at strengthening body resistance, eliminating pathogenic factors, regulating qi and blood, and restoring internal balance. The evidence for these applications was obtained from different study types. For instance, cell and animal studies were used mainly to support possible mechanisms related to tumor inhibition, metastasis prevention and drug-resistance reversal, whereas clinical studies were used to evaluate survival outcomes, treatment tolerance, postoperative recovery, and symptom improvement.

At the cellular and molecular levels, increasing evidence has shown that TCM -derived compounds can directly inhibit tumor growth and induce apoptosis. For example, baicalein, an active component of Scutellaria baicalensis, has been demonstrated to significantly inhibit the proliferation and colony formation of gastric cancer cells and to induce S-phase cell cycle arrest and apoptosis in a dose-dependent manner.^26,27 Mechanistic studies indicate that this effect may be associated with disruption of mitochondrial membrane potential, downregulation of Bcl-2, and upregulation of Bax, suggesting activation of the mitochondrial apoptosis pathway.²⁸ These findings are further supported by in vivo experiments showing clear tumor growth inhibition.⁴ However, the available evidence mainly supports pathway-level antitumor activity, and the direct primary molecular target of baicalein in gastric cancer remains to be further clarified. In addition to direct anti-tumor effects, TCM is also used in the postoperative management of gastric cancer, with the therapies aimed at strengthening resistance and promoting blood circulation to influence tumor-related biological markers and clinical outcomes. For instance, a study involving 63 postoperative gastric cancerpatients showed that, compared with Western medicine alone, combined treatment with TCM significantly reduced ornithine decarboxylase (ODC) levels, which are associated with tumor growth, invasion, and metastasis, and this reduction was correlated with improved prognosis.²⁹ These findings suggest that TCM may play a role in modulating tumor progression after surgery.

TCM has also been applied in the regulation of tumor metastasis and the tumor microenvironment. Spleen-tonifying and kidney-tonifying therapies, such as Jianpi Bushen treatment, have been shown in experimental models to inhibit the formation of the pre-metastatic niche in the lung by reducing the expression of key factors, including Rac1, Cdc42, SDF-1, and fibronectin (FN), thereby potentially limiting the establishment of metastatic lesions.³⁰ From a clinical perspective, a large retrospective cohort study conducted in Taiwan demonstrated that patients who received TCM treatment, including commonly used herbs such as Hedyotis diffusa and formulas such as Xiangsha Liujunzi Decoction, had significantly improved overall survival compared with non-users. Notably, patients who used TCM for more than 180 days showed a 63% reduction in mortality risk, suggesting a duration-dependent effect.³ Moreover, TCM has shown potential in enhancing the efficacy of chemotherapy and overcoming drug resistance. For example, the Zuojin Pill has been reported to reverse cisplatin resistance in gastric cancer cells by regulating the Rho-associated coiled-coil-containing protein kinase (ROCK)/phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K) signaling pathway, thereby promoting apoptosis both in vitro and in vivo.⁵ Similarly, Yangzheng Sanjie decoction has been shown to inhibit proliferation and induce apoptosis of gastric cancer cells through modulation of let-7a and c-Myc expression, indicating a role in the regulation of tumor-related gene expression.³¹

Taken together, these findings suggest that TCM may have multiple roles in gastric cancer management, but the strength of evidence differs by outcome. Direct inhibition of tumor growth, modulation of metastasis-related processes, and reversal of drug resistance are mainly supported by experimental studies, whereas improvement of postoperative outcomes and treatment tolerance has been evaluated in clinical studies.

Combination of TCM and Modern Medical Theory

The integration of TCM with modern medicine has become an important direction in gastric cancer research, as it provides a framework for interpreting the overall regulatory features of TCM through molecular targets, biological networks, and disease-related pathways. Unlike single-compound pharmacology, TCM formulas usually contain multiple active constituents that may act on several targets simultaneously. Therefore, systems pharmacology and network pharmacology have been widely used to analyze compound-target-pathway relationships and to generate hypotheses about possible mechanistic links between traditional therapeutic principles and modern biological processes. These approaches are useful for screening candidate active components, predicting potential targets, and mapping these targets onto pathways related to tumor progression, inflammation, metabolism, immune regulation, and treatment response. However, their findings are mainly predictive and depend on database quality, target annotation, algorithm selection, and pathway enrichment methods. Therefore, network-based results should not be interpreted as direct mechanistic proof unless they are further supported by experimental validation and, ideally, clinical biomarker data. For example, a systems pharmacology study of Compound Saffron Formula systematically screened its active ingredients and corresponding targets, and identified 103 potential active components and 219 direct targets.¹⁰ On this basis, the authors constructed interaction networks among compounds, targets, and diseases, and further incorporated disease-related pathway modules to explain how the formula may exert regulatory effects on different pathological processes at multiple levels. Although this study was not conducted in gastric cancer, it provides a methodological example of how systems-level analysis can be used to examine the pharmacological basis of compound TCM formulas. Similarly, network pharmacology has been used to explore the molecular basis of TCM prescriptions by identifying active ingredients, core targets, and related signaling pathways. A study on the Jianpi Huatan Quyu recipe identified 227 active ingredients, among which quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, and isorhamnetin were considered key active compounds.³² These ingredients were predicted to regulate multiple targets, including STAT3, MAPK3, AKT1, JUN, MAPK1, TP53, TNF, IL6, and EGFR, and were associated with pathways such as PI3K-Akt, HIF-1, IL-17, NF-κB, cAMP, and AMPK signaling pathways. Although this study focused on chronic heart failure rather than gastric cancer, it illustrates how network pharmacology can clarify the potential biological basis of TCM prescriptions through compound-target-pathway analysis. For gastric cancer research, this type of approach may help explain how TCM formulas exert multi-target effects related to tumor cell survival, inflammatory regulation, immune modulation, and metabolic reprogramming, while also providing candidate targets for further experimental validation.

Modern biomedical technologies, including metabolomics and serum pharmacology, have provided new approaches for investigating the pharmacological basis of TCM. For instance, serum pharmacology allows the preparation of medicated serum containing bioavailable components of TCM formulas, thereby enabling functional evaluation in vitro. A study on Yangzheng Sanjie decoction demonstrated that its medicated serum could significantly inhibit the proliferation of gastric cancer cells and induce apoptosis, which was associated with upregulation of let-7a expression and downregulation of c-Myc, suggesting a regulatory effect on tumor-related gene expression.³¹ In addition, the “chinmedomics” strategy, which integrates serum pharmacochemistry with metabolomics, has been proposed as a method to link TCM theory with measurable biological changes. Using this approach, studies on Shenqi pills identified multiple endogenous metabolic biomarkers and their associated active components, and further analysis suggested that these components may exert therapeutic effects through the regulation of pathways related to steroid hormone metabolism, tryptophan metabolism, and thyroid hormone function.³³ This type of integrative analysis provides a more direct connection between the chemical basis of TCM formulas, syndrome-related metabolic changes, and their biological effects. Furthermore, the development and evaluation of clinical practice guidelines for integrated traditional Chinese and Western medicine have continued to progress. Assessment of TCM-related guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool has shown that, although the number of guidelines has increased, their overall methodological quality remains variable, and only a proportion have been developed based on evidence-based approaches; however, structured evaluation frameworks such as AGREE II provide a basis for improving their quality and standardization.³⁴

Collectively, these findings indicate that the application of modern biomedical technologies not only facilitates a better understanding of the pharmacological basis of TCM but also contributes to the standardization and clinical translation of TCM practices. In gastric cancer, such integration provides a practical framework for linking traditional theory with modern experimental evidence, thereby supporting the development of more rational and evidence-informed therapeutic strategies. The conceptual framework underlying TCM-based therapy for gastric cancer is summarized in Figure 1.

Figure 1.

Conceptual framework of traditional Chinese medicine-based therapy for gastric cancer. This figure illustrates the conceptual framework underlying TCM-based therapy for gastric cancer. The left panel summarizes the major pathogenic mechanisms of gastric cancer, including dysregulated proliferation and apoptosis, an immunosuppressive tumor microenvironment, non-coding RNA dysregulation, and chronic inflammation associated with Helicobacter pylori infection. The central panel highlights the key mechanisms of TCM intervention, encompassing mitochondria-mediated apoptosis, reversal of drug resistance, inhibition of tumor metabolism, and suppression of epithelial-mesenchymal transition and metastatic processes, together with representative therapeutic strategies such as Fuzheng therapy, which aims to support host resistance; Qingre Jiedu therapy, which aims to clear heat-related inflammatory or toxin-like pathological states; and Yiqi Huoxue therapy, which aims to support functional activity and improve blood circulation. The right panel emphasizes the integration of TCM with modern medical approaches, including network and systems pharmacology, omics technologies, serum pharmacology, nanotechnology-based drug delivery systems, and the development of clinical evidence and practice guidelines.

Clinical Practice of TCM in the Treatment of Gastric Cancer

Clinical studies on TCM in gastric cancer have mainly evaluated its use as an adjunctive approach in advanced disease, perioperative care, and the management of treatment-related adverse effects, suggesting possible benefits in survival, functional status, treatment tolerance, postoperative recovery, and symptom control. However, the strength of evidence varies considerably across interventions and outcomes. Some studies are randomized trials or meta-analyses, whereas others are retrospective, single-center, or observational studies, and therefore their findings should be interpreted according to study design, sample size, intervention heterogeneity, and risk of confounding. In this context, the available clinical evidence supports further evaluation of TCM as a complementary strategy, but it does not establish uniform efficacy across all formulas, disease stages, or clinical settings. For instance, in patients with advanced gastric cancer, TCM has often been used as an adjunct to chemotherapy to improve survival, maintain functional status, and enhance treatment tolerance. A retrospective study involving 182 patients with stage IV non-surgical gastric cancer showed that the median overall survival in the integrated traditional Chinese and Western medicine group was 16.9 months, which was significantly longer than the 10.5 months observed in the chemotherapy-alone group. In the same study, the 1-, 3-, and 5-year survival rates were 70%, 18%, and 11%, respectively, in the integrated treatment group, compared with 32%, 4%, and 0% in the chemotherapy-alone group. In addition, Karnofsky performance status after six months of treatment was also better in the integrated treatment group, suggesting that the combination of TCM with chemotherapy may provide benefit not only in survival but also in quality of life and general functional condition.⁶ A similar trend was observed in a randomized clinical trial evaluating Bo-Er-Ning capsule (BENC) as an add-on treatment for advanced gastric cancer. In that study, BENC combined with chemotherapy improved Karnofsky performance scores and 3-year overall survival compared with conventional chemotherapy alone. The authors further used bioinformatics-assisted analysis and experimental validation to show that the potential effects of BENC were related to the regulation of biological processes such as cell proliferation, cell cycle progression, and apoptosis.³⁵ These studies suggest that TCM may have practical value in the clinical treatment of advanced gastric cancer, especially when used in combination with standard systemic therapy.

In addition to its potential influence on survival outcomes, TCM has also been applied to reduce adverse reactions associated with chemotherapy and to improve treatment tolerance. A multicenter randomized controlled trial investigated Xiaoaiping injection for chemotherapy-induced thrombocytopenia in patients with non-small cell lung cancer and gastric cancer. The study showed that platelet counts in the intervention group exhibited a significant upward trend by day 21, and no significant differences were observed between the two groups in measured safety indicators, including liver function, kidney function, and hematologic parameters.³⁶ However, it should also be noted that the subgroup analysis in the abstract showed a significant platelet benefit in patients with non-small cell lung cancer, whereas no statistically significant difference was observed in the gastric cancer subgroup during the trial period.³⁶ In parallel, Jianpi Yangzheng Xiaozheng Decoction has been investigated in a prospective multicenter randomized controlled trial protocol for advanced gastric cancer, with primary outcomes including one-year survival, progression-free survival, and overall survival, and secondary outcomes including immune-related hematologic indices, tumor markers, TCM syndrome scores, fatigue, and quality of life.³⁷ Since this publication is a study protocol rather than a completed trial, it does not provide direct evidence of clinical efficacy, but it reflects the increasing effort to evaluate TCM in gastric cancer through more structured clinical research.

TCM has also been increasingly used in the postoperative management of gastric cancer, where patients frequently experience pain, delayed gastrointestinal recovery, nutritional impairment, and immune dysfunction. In a randomized controlled trial, transcutaneous electrical acupoint stimulation (TEAS) was shown to provide effective pain relief after gastrectomy, reduce pain scores during postoperative days 1 to 5, lower opioid use, promote earlier first flatus and defecation, reduce postoperative nausea, and improve tolerance to semi-fluid diet, without reported adverse events.⁷ These findings suggest that TEAS could be a useful adjunctive intervention to enhance postoperative recovery. In addition, a study of modified Pingwei Baohe Decoction in postoperative gastric cancer patients showed that this intervention could improve immune function, reduce inflammatory responses, improve nutritional status, and accelerate gastrointestinal recovery, including shorter times to first flatus, bowel sound recovery, and relief of abdominal distension.⁸ TCM nursing interventions have also shown potential value in this setting. A randomized study of postoperative gastric cancer patients found that TCM nursing was associated with earlier recovery of gastrointestinal function, lower levels of inflammatory markers such as tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-1β (IL-1β), improved anxiety and depression scores, better self-esteem and quality-of-life scores, and a lower incidence of adverse reactions during hospitalization.³⁸ These studies indicate that the role of TCM in clinical practice extends beyond antitumor treatment alone and includes supportive care during the perioperative period.

In the setting of combination therapy, the combination of TCM with chemotherapy has also been associated with improvements in immune function, coagulation-related indices, and long-term survival. For instance, a study involving 69 patients with postoperative mid- or late-stage gastric cancer showed that Fuzheng Huoxue anticancer prescription significantly improved T-lymphocyte immune function, normalized the OKT4/OKT8 ratio, improved antithrombin III concentration and fibrinolytic activity, and increased the 1-, 3-, and 5-year survival rates to 86%, 69%, and 40%, respectively, which were all higher than those in the control group.³⁹ In addition, the corresponding animal experiments suggested a direct inhibitory effect on tumor growth without obvious toxic side effects.³⁹ Similarly, a nationwide retrospective matched-cohort study showed that complementary Chinese herbal medicine use was associated with a lower mortality risk in patients with gastric cancer, with an adjusted hazard ratio of 0.55 overall and 0.37 in those who used Chinese herbal medicine for more than 180 days per year.³ The Kaplan-Meier analysis in that study also showed higher survival probability in Chinese herbal medicine users, further supporting the potential clinical value of long-term adjunctive TCM use.

Another clinically relevant aspect is the potential of TCM to improve chemotherapy sensitivity and reduce treatment-related toxicity. Experimental studies have shown that curcumin, when co-delivered with 5-fluorouracil (5-FU), can enhance the antitumor effect of 5-FU, help overcome chemotherapy resistance, and induce apoptosis through a mechanism associated with reactive oxygen species and mitochondrial dysfunction.⁴⁰ Similarly, the decoction Zuojinwan has been shown to reverse cisplatin resistance in gastric cancer through regulation of the ROCK/PTEN/PI3K signaling pathway, and combined treatment with cisplatin and Zuojinwan significantly reduced tumor growth in vivo compared with cisplatin alone.⁵ In addition, evidence from a meta-analysis of 27 randomized controlled trials showed that cinobufotalin combined with chemotherapy improved overall response rate, disease control rate, quality of life, and pain relief, while also reducing multiple chemotherapy-related adverse reactions, including leukopenia, anemia, gastrointestinal side effects, and peripheral neurotoxicity.⁴¹ Taken together, the clinical evidence supports several potential complementary roles of TCM in gastric cancer management, including adjunctive treatment, improvement of treatment tolerance, and postoperative rehabilitation. However, reversal of chemotherapy resistance remains mainly supported by experimental evidence and should be interpreted as a mechanistic possibility that requires clinical confirmation. The complementary applications of TCM across multiple aspects of gastric cancer management, including survival improvement, toxicity reduction, and perioperative support, are summarized in Figure 2.

Figure 2.

Clinical practice of traditional Chinese medicine in the management of gastric cancer. This schematic illustrates the clinical roles of TCM in the management of gastric cancer. Integration of TCM with conventional treatments has been associated with improved therapeutic efficacy and survival-related outcomes in some studies, including prolonged overall and progression-free survival, enhanced performance status, and increased long-term survival rates. TCM also contributes to the reduction of chemotherapy-related toxicities, leading to improved treatment tolerance and quality of life. In addition, TCM provides perioperative and supportive care benefits, such as postoperative pain relief, modulation of immune and inflammatory responses, and enhanced recovery through nursing interventions.

Technical Progress on TCM in the Treatment of Gastric Cancer

Technical progress in TCM for gastric cancer is mainly reflected in the identification of active compounds, mechanistic validation, development of candidate agents and formulas, and improvement of pharmaceutical preparation and delivery systems. In recent years, the application of modern experimental and analytical methods has made it possible to investigate TCM from the perspectives of chemical composition, molecular targets, signaling pathways, and formulation technology. However, it is important to distinguish between findings derived from preclinical studies and evidence that may have more direct clinical relevance, because many of the currently available data in this field still come primarily from in vitro experiments, animal models, and technology-development studies rather than from clinical trials.

At the level of active compounds, most current evidence remains preclinical. A growing number of cell-based and animal studies have shown that TCM-derived compounds can regulate biological processes relevant to gastric cancer, including apoptosis, proliferation, invasion, and related signaling pathways. For example, baicalein has been reported in preclinical studies to induce apoptosis in gastric cancer cells through the mitochondrial pathway, accompanied by downregulation of Bcl-2 and upregulation of Bax and cleaved caspase-3.⁴ In addition to its effects on apoptosis, baicalein has also been shown to inhibit the proliferation of gastric cancer cells by regulating histone H3K27me3 demethylase KDM6B and affecting succinate metabolism.⁴² Similarly, resveratrol has been shown in experimental models to inhibit the migration and invasion of gastric cancer cells by suppressing MALAT1-mediated epithelial-mesenchymal transition.⁴³ These findings provide useful mechanistic support for the anti-gastric cancer potential of TCM-derived compounds, but they should be understood primarily as preclinical evidence rather than direct proof of clinical efficacy.

Progress has also been made in the mechanistic investigation of TCM formulas. For example, Jianpi Bushen therapy has been reported in a murine model of spontaneous lung metastasis to suppress pre-metastatic formation by reducing the expression of Rac1, Cdc42, SDF-1, and fibronectin.³⁰ This study is important because it suggests that certain TCM formulas may affect metastasis-related processes at an early stage, but its findings remain experimental in nature. Meanwhile, network pharmacology and molecular docking have provided useful technical tools for analyzing the active compounds, potential targets, and relevant pathways of complex TCM formulas. For instance, studies on the combination of Coptis chinensis, Pinellia ternata, and Scutellaria baicalensis identified multiple active compounds and hub targets, including EGFR, PTGS2, STAT3, MAPK3, MAPK8, and MTOR, and linked them to pathways related to H. pylori-associated inflammation and carcinogenesis.⁴⁴ In the same study, animal experiments showed that this core combination could eradicate H. pylori, alleviate gastric pathological injury, and reduce TNF-α and IL-1β levels in the gastric mucosa.⁴⁴ This work provides useful technical and mechanistic insight into how TCM formulas can be studied in gastric carcinogenesis.

The development of new therapeutic agents from TCM has become another important area of technical progress, although the available evidence in this field is also largely preclinical. Current studies focus on identifying active compounds or formula-derived components with anti-gastric cancer activity and on exploring whether they can improve sensitivity to existing anticancer drugs. For example, berberine has been shown in cisplatin-resistant gastric cancer cell lines to reverse cisplatin resistance by upregulating miR-203 and downregulating Bcl-w, thereby promoting caspase-dependent apoptosis.⁴⁵ Similarly, Astragalus polysaccharide has been reported in AGS gastric cancer cells to enhance the antitumor effect of apatinib by inhibiting AKT signaling, suppressing proliferation, migration, and invasion, and increasing apoptosis.⁴⁶ These studies suggest that TCM-derived compounds may have potential as drug sensitizers or adjunctive agents, but these observations are still based on experimental models and require further validation before clinical implications can be firmly established.

Further technical progress has also been observed in studies of TCM-based formulas. The Yangzheng Sanjie decoction has been shown in gastric cancer cells to inhibit proliferation and induce apoptosis through upregulation of let-7a and downregulation of c-Myc.³¹ In addition, Yang Wei Shu granule has been investigated using a combination of ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS), network pharmacology, molecular docking, and cell experiments, through which 150 compounds and 47 blood-entry constituents were identified, and several potential targets, including AKT1, PIK3CA, PTPN11, SRC, and STAT3, were screened.⁴⁷ Cellular experiments further showed that Yang Wei Shu granule-containing serum could inhibit nitric oxide production and reduce the expression of pro-inflammatory factors such as TNF-α, IL-6, and IL-1β, while increasing IL-10 expression.⁴⁷ In addition to studies on compounds and formulas, technical progress has also been observed in improvements in preparation and delivery systems. These advances are particularly important because many TCM-derived compounds have limitations such as poor solubility, low bioavailability, or insufficient targeting ability. Jinlong capsules, prepared using low-temperature biochemical separation technology, have been shown in preclinical studies to inhibit the proliferation of gastric cancer cells by inducing apoptosis and to suppress tumor growth in vivo.⁴⁸ Similarly, a cellulose-based microgel/hydrogel co-delivery system containing 5-fluorouracil and curcumin has recently been developed for gastric cancer treatment, which achieved sustained dual-drug release, enhanced the antitumor effect of 5-FU, helped overcome chemotherapy resistance, and showed good biocompatibility in preclinical evaluation.⁴⁰ These results indicate that modern biomaterial and delivery technologies may improve the applicability of TCM-derived agents, although these approaches remain at the experimental development stage.

Nanotechnology-based delivery systems have further promoted the modernization of TCM in gastric cancer research. For example, a vascular endothelial growth factor receptor 3 (VEGFR-3) antibody-conjugated ginsenoside Rg3 nanoemulsion was shown in an orthotopic mouse model of human gastric cancer to inhibit primary tumor growth and reduce lymph-node metastasis, while also suppressing the expression of vascular endothelial growth factor C (VEGF-C), vascular endothelial growth factor D (VEGF-D), and VEGFR-3 without obvious toxicity.⁹ In addition, protein-based nanocarriers have been explored as delivery platforms for TCM-derived compounds such as curcumin to improve intracellular uptake and drug-targeting efficiency.⁴⁹ Similarly, pH-responsive alginate microspheres loaded with puerarin have shown improved retention time, site-specific release, and anti-tumor efficacy in a model of colitis-associated colorectal cancer.⁵⁰

Taken together, recent technical advances have improved the study of TCM in gastric cancer by clarifying the material basis of active compounds, identifying potential targets and pathways, supporting the development of candidate drugs and formulas, and improving formulation and delivery strategies. At the same time, most of the mechanistic evidence discussed in this section remains preclinical, whereas direct clinical evidence for these specific technical advances remains limited. Therefore, these should be viewed as providing an important experimental and technical foundation for future translation, rather than as definitive proof of clinical benefit. For TCM-derived compounds or formula-based preparations to move toward oncology drug development, several translational requirements still need to be addressed, including batch-to-batch consistency, identification of active and quality-control components, pharmacokinetic and biodistribution evaluation, dose-response characterization, herb-drug interaction assessment, and systematic acute and long-term toxicity testing. In addition, candidate preparations should be evaluated through standardized manufacturing processes and stepwise clinical validation before they can be considered for broader clinical application. The ongoing transition of TCM research from empirical application toward mechanism-based investigation and technological optimization, and the major technical advances discussed are summarized in Figure 3.

Figure 3.

Technical advances in TCM-based therapy for gastric cancer. This schematic summarizes the major technical advances in TCM-based therapy for gastric cancer. Key progress includes mechanistic elucidation of TCM components, drug discovery and optimization, formulation modernization, and nanotechnology-based delivery systems. These advances may support therapeutic optimization, reduce systemic toxicity, and facilitate the translational development of TCM-based interventions in gastric cancer treatment.

Patterns of TCM Use, Patient Acceptance, and Observational Outcomes in Gastric Cancer

Studies on TCM use in gastric cancer have mainly focused on real-world application patterns, treatment duration, patient acceptance, regional practice differences, and observational associations with clinical outcomes. These studies are relevant to clinical implementation, but they should not be confused with classical epidemiological studies of gastric cancer incidence, prevalence, risk factors, or global disease burden. A retrospective cohort study conducted in Taiwan included 1333 patients with gastric cancer, of whom 962 received TCM treatment, and showed that the risk of death was significantly reduced among TCM users. In that study, a longer duration of TCM use was associated with a greater reduction in risk, with a 63% decrease in mortality observed among patients who used TCM for more than 180 days.³ In addition, differences in the application of TCM across regions have also been reported. For example, Agastache rugosa essential oil from the Xinjiang region has shown cytotoxic effects on gastric cancer SGC-7901 cells, with its mechanism related to the induction of apoptosis.⁵¹ Although these findings suggest a possible association between TCM exposure and survival-related outcomes, their observational nature means that potential confounding and treatment-selection bias should be considered.

The clinical characteristics of patients receiving TCM may also influence the observed outcomes. For instance, Jianpi Bushen Decoction combined with chemotherapy has been reported to improve disease-free survival in patients with stage III gastric cancer,⁵² whereas Yiqi Huoxue Jiedu Decoction has been investigated for reducing the risk of recurrence and metastasis after surgery.⁵³ These studies suggest that TCM may be used in different clinical settings, including postoperative management, chemotherapy support, and recurrence-risk reduction. However, the interpretation of these findings should take into account differences in tumor stage, treatment background, TCM formula selection, treatment duration, and outcome definition.

Patient acceptance is another important aspect of TCM use in gastric cancer. A study conducted in China indicated that patients with gastric cancer generally showed a high level of acceptance of TCM, particularly during chemotherapy, because it may help alleviate treatment-related adverse effects and improve quality of life.⁵⁴ For example, Xiaoaiping injection has been reported to increase platelet counts in patients undergoing chemotherapy,³⁶ whereas Shenqi Fuzheng injection can improve chemotherapy-induced leukopenia.⁴¹ These effects may partly explain why some patients are willing to use TCM as an adjunctive treatment during conventional cancer therapy.

Individualized treatment based on TCM syndrome differentiation may further influence treatment acceptance and clinical use. Prescriptions such as Xiangsha Liujunzi Decoction and Buzhong Yiqi Decoction can be adjusted according to the specific syndrome type of each patient, which may improve treatment suitability in routine practice.³ A survey also indicated that acceptance of TCM among patients with gastric cancer is associated with factors such as age, educational level, and economic status, with higher acceptance observed among patients of older age, higher educational attainment, and better economic conditions.⁵⁵ These findings suggest that the use of TCM is influenced not only by clinical factors but also by social, cultural, and economic background.

There are also clear regional differences in the application of TCM in gastric cancer, which are related to variations in cultural background, medical practice, and the availability of medicinal resources. For example, patients with gastric cancer in Taiwan commonly use TCM treatments such as Hedyotis diffusa and Xiangsha Liujunzi Decoction,³ whereas local medicinal materials such as Agastache rugosa are more frequently used in Xinjiang.⁵¹ In addition, differences in syndrome differentiation have been observed between regions; patients in northern areas are more often characterized by spleen-stomach deficiency-cold syndromes, whereas those in southern regions are more commonly associated with damp-heat accumulation patterns.⁵⁶ These variations reflect differences in medical practice, local resources, cultural background, and clinical experience.

Regional practice differences are also reflected in treatment strategies. For example, patients in Japan and South Korea are more likely to use classical Chinese medicine formulas such as Xiaochaihu Decoction and Banxia Xiexin Decoction,⁵⁶ whereas in China, greater emphasis is placed on compound prescriptions such as Jianpi Fuzheng Xiaozheng Decoction and Yiqi Huoxue Jiedu Decoction.^37,53 These differences highlight the adaptability of TCM across different healthcare settings, but they also create challenges for standardization, comparative evaluation, and generalization of findings across populations (Figure 4).

Figure 4.

Application patterns and observational outcomes of TCM in gastric cancer. This figure summarizes the main factors related to TCM exposure in patients with gastric cancer. Population heterogeneity includes age, educational level, economic status, and clinical stage. Exposure characteristics include the reported prevalence of TCM use, treatment duration of more than 180 days, combined use with chemotherapy, and syndrome differentiation. Outcome impact includes observational associations with reduced mortality risk, improved disease-free survival, reduced recurrence, and fewer adverse effects. These findings should be interpreted as real-world observational associations rather than definitive evidence of causal treatment efficacy. ↑ indicates increase. ↓ indicates decrease. 180d indicates 180 days.

In addition, most available clinical and real-world evidence on TCM in gastric cancer has been derived from Asian populations, and therefore, the generalizability of these findings to Western or other non-Asian populations remains uncertain. Differences in ethnicity, dietary background, gut microbiome composition, tumor biology, healthcare systems, and the availability of trained TCM practitioners may influence both treatment response and patient acceptance. For this reason, TCM interventions used in Asian cohorts may require further clinical validation and appropriate adaptation before being applied more broadly in non-Asian populations. Future studies should include more diverse populations and should evaluate whether syndrome differentiation, formula selection, treatment duration, and combination strategies need adjustment across different clinical and cultural settings.

In summary, real-world and observational evidence indicate that the use of TCM in gastric cancer is associated with differences in survival-related outcomes, patient acceptance, and treatment patterns across populations and regions. As most of these studies are observational, they should be interpreted as real-world evidence supporting clinical associations rather than definitive proof of treatment efficacy. These findings nevertheless support the potential role of TCM as a complementary and adaptable approach in the comprehensive gastric cancer management.

Controversies and Challenges of TCM in the Treatment of Gastric Cancer

The scientific controversy surrounding the use of TCM in the treatment of gastric cancer mainly relates to the limited strength of clinical evidence, incomplete mechanistic clarification, safety concerns, and insufficient standardization of syndrome differentiation, formula preparation, and efficacy evaluation. Although numerous studies have reported potential anti-gastric cancer effects of TCM, some of the available clinical studies are still constrained by small sample sizes, single-center designs, heterogeneous interventions, and variable outcome measures. For example, a meta-analysis of 27 randomized controlled trials showed that cinobufacini combined with chemotherapy improved the overall response rate in patients with gastric cancer; however, several included studies were reported as having relatively low methodological quality.⁴¹ Therefore, future clinical studies should move beyond simply comparing “TCM plus conventional treatment” with conventional treatment alone, and should instead adopt clearer intervention definitions, standardized treatment duration, prespecified endpoints, and appropriate follow-up periods. Multicenter randomized controlled trials and prospective cohort studies with transparent allocation, treatment adherence assessment, adverse-event monitoring and stratification by tumor stage and treatment background would also provide more reliable evidence for determining which patients are most likely to benefit from adjunctive TCM.

Another major challenge is that the multi-component and multi-target nature of TCM makes mechanistic interpretation difficult. Unlike single-agent anticancer drugs, TCM formulas may influence several biological processes simultaneously, including apoptosis, inflammation, immune regulation, metabolism, angiogenesis, and drug resistance.⁵⁷ Modern approaches such as systems pharmacology, network pharmacology, molecular docking, metabolomics, and chinmedomics have provided useful tools for identifying active components, predicted targets, and disease-related pathways. For instance, network pharmacology analysis has shown that the active components of Jianpi Huatan Quyu Fang may act on targets such as STAT3 and MAPK3 and participate in multiple signaling pathways,³² while chinmedomics can be used to identify active compounds and their corresponding biological effects in TCM formulas.³³ However, these methods should be regarded as hypothesis-generating rather than confirmatory. To make mechanistic research more convincing, predicted targets should be further examined using cell experiments, animal models, patient-derived samples, and, when possible, clinical biomarker data. In gastric cancer, this means that candidate mechanisms should be linked not only to pathway enrichment results, but also to measurable changes in tumor biology, immune cell populations, inflammatory mediators, metabolic profiles, treatment response, or postoperative recovery.

The safety of TCM in the treatment of gastric cancer is another important consideration for its clinical application. Many studies have suggested that TCM is generally associated with a relatively low incidence of adverse reactions, and some TCM interventions may reduce treatment-related toxicity when combined with chemotherapy. For example, Jinlong capsules have not shown significant toxicity in in vivo studies,⁴⁸ and Xiaoaiping injection has not been associated with significant liver or kidney dysfunction in clinical trials.³⁶ In addition, the combination of TCM with chemotherapy may help reduce treatment-related adverse effects; for instance, Shenqi Fuzheng injection has been reported to decrease the incidence of chemotherapy-induced leukopenia.⁴¹ Nevertheless, treatment safety cannot be assumed simply because an intervention is derived from traditional practice. Certain components, such as aristolochic acid, are known to be nephrotoxic and must be strictly avoided.⁵⁸ In addition, the complex composition of herbal formulas may influence absorption, metabolism, efficacy, and toxicity when used together with chemotherapy, targeted therapy, immunotherapy, anticoagulants, analgesics, or nutritional support. Thus, future studies should include systematic component identification, quality-control testing, contaminant and adulterant screening, pharmacokinetic analysis, herb-drug interaction assessment, and both short-term and long-term toxicity evaluation. These requirements are important in cancer treatment as patients often receive multiple drugs and may have impaired nutritional, hepatic, renal, or immune function.

Another key challenge lies in the standardization of TCM in the treatment of gastric cancer, which involves the standardization of syndrome differentiation, evaluation of therapeutic effects, and quality of medicinal materials. At present, there remains a lack of a widely accepted system for syndrome differentiation, and different researchers may adopt different classification approaches; for example, some classify gastric cancer syndromes as spleen-stomach deficiency-cold type and damp-heat accumulation type, whereas others classify them as qi and yin deficiency, blood stasis, and toxin accumulation types.⁵⁶ In addition, the evaluation of TCM efficacy often relies on subjective indicators, such as syndrome scores, while objective biological markers remain insufficient.¹¹ This heterogeneity makes it difficult to compare studies, reproduce interventions, or generalize findings across populations. To address this issue, future research should use consensus-based syndrome criteria, report the diagnostic basis for syndrome differentiation in detail, and describe formula composition, dosage, preparation method, treatment duration, and modification rules transparently. The development of TCM syndrome scales using methods such as the Delphi approach provides a useful foundation,⁵⁹ but these tools still require broader validation in independent gastric cancer cohorts.

At the same time, standardization should not remove the individualized nature of TCM treatment. A more practical approach is to establish a reproducible core framework while allowing limited and clearly recorded formula modification according to patient symptoms, disease stage, treatment phase, and tolerance. The use of objective markers may also help improve the reproducibility of syndrome classification and treatment monitoring. In this regard, chinmedomics and metabolomics may provide auxiliary evidence by identifying metabolic patterns related to specific syndrome types,⁶⁰ although these methods cannot replace traditional assessment based on symptoms, tongue, pulse, and clinical judgment. For example, spleen-stomach deficiency-cold syndrome could be investigated through serum, urine, or fecal metabolomic profiles, with attention to pathways related to energy metabolism, amino acid metabolism, lipid metabolism, inflammatory regulation, and gut microbiota-derived metabolites.⁶¹ If reproducible features are confirmed in multicenter cohorts, they may serve as supportive markers for syndrome classification, formula selection, and therapeutic monitoring. However, standardized sampling, analytical methods, data processing procedures, and external validation are required before such markers can be used in routine clinical practice.

The evaluation of therapeutic effects also requires further refinement. In many studies, efficacy assessment relies on tumor response, survival, symptom scores, or TCM syndrome scores, but the relationship among these outcomes is not always clear. Future studies should combine oncological endpoints, such as overall survival, progression-free survival, recurrence, treatment response, and adverse events, with patient-centered outcomes, including postoperative recovery, nutritional status, fatigue, gastrointestinal symptoms, quality of life, and treatment tolerance. For perioperative and supportive-care interventions, outcomes such as time to flatus, postoperative pain, opioid use, inflammatory markers, length of hospital stay, and recovery of oral intake may be more clinically relevant than tumor response alone. This outcome selection should match the intended role of the TCM intervention, whether it is used for antitumor support, toxicity reduction, postoperative rehabilitation, immune regulation, or symptom control.

Quality control of TCM preparations is also essential for clinical translation. The chemical composition of herbal medicines may vary according to plant origin, cultivation environment, harvesting time, processing method, storage condition, and manufacturing process. Without adequate quality control, the reproducibility of clinical and experimental findings remains limited. Network pharmacology has been explored for establishing quality-control standards for TCM formulas,⁵⁷ and national guidelines have also attempted to standardize syndrome differentiation, treatment principles, and prescription selection.¹² However, future translational studies should further define active or marker components, establish batch-to-batch consistency, and connect quality-control indicators with biological activity and clinical outcomes. This would help move TCM research from empirical formula use toward more reproducible and evidence-informed application. The key controversies and challenges discussed above are summarized in Figure 5.

Figure 5.

Controversies and challenges of traditional Chinese medicine in the treatment of gastric cancer. This figure summarizes the major controversies and challenges associated with the use of TCM in gastric cancer treatment, including limitations in high-quality clinical evidence, mechanistic ambiguity due to multicomponent and multitarget characteristics, safety and quality concerns, and a lack of standardization in syndrome differentiation and efficacy evaluation. These issues highlight the need for rigorous clinical studies, comprehensive safety assessment, and standardized evaluation systems to support the rational clinical application of TCM.

Taken together, the controversies surrounding TCM in gastric cancer should not be viewed only as obstacles, but also as directions for improving future research. High-quality clinical trials, standardized syndrome differentiation, objective auxiliary biomarkers, rigorous safety assessment, reproducible formula preparation, and mechanism-oriented validation are all needed to clarify the role of TCM in gastric cancer management. With these improvements, TCM may be more appropriately integrated into evidence-based oncology as a complementary approach for selected patients, particularly in treatment tolerance, postoperative recovery, symptom management, and individualized supportive care.

Prospect of TCM in the Treatment of Gastric Cancer

Potential future directions for TCM in the treatment of gastric cancer include its integration into targeted therapy, immunotherapy, and personalized treatment strategies. In regards to targeted therapy, certain TCM-derived compounds, such as curcumin and berberine, have been investigated as potential agents that exert antitumor effects through the regulation of specific signaling pathways.^40,45 With respect to immunotherapy, TCM may enhance anti-tumor immune responses by modulating the tumor immune microenvironment; for example, Astragalus polysaccharide has been reported to enhance the anti-gastric cancer effect of apatinib through inhibition of the AKT signaling pathway.⁴⁶

Personalized treatment represents an important characteristic of TCM, and when combined with modern molecular diagnostic techniques, it may contribute to more precise therapeutic approaches. For instance, treatment strategies can be adjusted based on gene expression profiles in patients with gastric cancer, allowing for the selection of appropriate TCM formulations.¹⁴ In addition, the integration of TCM with modern medical approaches provides opportunities for the development of novel therapeutic strategies, such as combining TCM-derived compounds with immune checkpoint inhibitors to potentially enhance treatment efficacy.¹³ These developments suggest a broad scope for the application of TCM in the management of gastric cancer.

The combination of TCM with immunotherapy has received increasing attention, particularly in relation to its potential role in modulating the immune microenvironment and enhancing the effectiveness of immunotherapeutic agents. For example, Astragalus polysaccharide has also been reported to enhance T-cell-mediated anti-tumor responses through downregulation of programmed death-ligand 1 (PD-L1) expression,¹³ while ginsenoside Rg3 may inhibit lymphatic metastasis of gastric cancer by reducing the expression of VEGF-C, VEGF-D, and VEGFR-3.⁹ In addition, TCM may help improve the immunosuppressive tumor microenvironment by regulating immune cell populations, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs).^1,62

Several preclinical and early clinical studies have suggested that combining TCM with immunotherapy may improve therapeutic outcomes in gastric cancer, but clinical evidence for TCM combined with immune checkpoint inhibitors remains limited, and this strategy still requires validation in well-designed prospective trials. For example, the combination of Jianpi Bushen Fang with a PD-1 inhibitor has been associated with an improved objective response rate in patients with gastric cancer,¹³ while the use of TCM compounds such as curcumin in combination with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors has been reported to enhance anti-tumor immune responses.⁶² Although these findings are encouraging, further validation in well-designed clinical studies is still required.

TCM has also shown potential in the personalized management of gastric cancer, where treatment is tailored according to syndrome differentiation, molecular characteristics, and immune status. For example, individualized prescriptions based on TCM syndrome differentiation allow for the selection of appropriate formulas, such as Xiangsha Liujunzi Decoction for spleen-stomach deficiency-cold syndrome and Huanglian Jiedu Decoction for damp-heat accumulation patterns.³ When combined with modern diagnostic techniques, including gene sequencing and immunohistochemistry, these approaches may further refine treatment selection.¹⁴

In addition, emerging approaches based on network pharmacology have been used to predict the therapeutic effects of TCM formulas according to gene expression profiles in patients with gastric cancer.⁵⁷ The integration of TCM with modern targeted therapies also provides opportunities for developing personalized treatment strategies, such as selecting appropriate drug combinations based on specific gene mutations.⁶³ Together, these findings indicate that TCM may contribute to the development of more individualized treatment approaches in gastric cancer (Figure 6).

Figure 6.

Prospects of traditional Chinese medicine in the treatment of gastric cancer. This schematic illustrates the future directions of TCM in gastric cancer treatment, including targeted therapy-oriented TCM, integration with immunotherapy, and personalized and precision TCM therapy. Modulation of oncogenic signaling pathways and the tumor immune microenvironment, as well as integration with molecular diagnostics and network pharmacology, may support future studies on precision medicine and combination therapeutic strategies for gastric cancer, although further clinical validation remains necessary.

Collectively, the future development of TCM in gastric cancer is likely to focus on its integration with targeted therapy, immunotherapy, and molecular diagnostics, with particular potential in personalized treatment approaches; however, further high-quality clinical evidence is needed to support its clinical application and optimize its role within modern oncological practice.

Conclusions

Gastric cancer remains a complex disease that requires comprehensive and multidisciplinary management. This review summarizes current evidence on TCM in gastric cancer, including its theoretical basis, mechanistic findings, clinical applications, technical advances, and translational challenges. Overall, TCM may have a complementary role in gastric cancer care, particularly in supportive treatment, postoperative recovery, symptom relief, and improvement of treatment tolerance. However, the current evidence should be interpreted cautiously, as the strength of support varies across study designs, interventions, and outcomes. At present, clinical evidence is relatively more applicable to adjunctive and supportive settings, whereas direct antitumor effects, reversal of chemotherapy resistance, integration with immunotherapy or targeted therapy, and precision TCM remain largely exploratory. Many mechanistic findings are derived from cell experiments, animal models, network pharmacology, molecular docking, and omics-based studies, and therefore require further experimental confirmation and clinical validation. In addition, many clinical studies are limited by small sample sizes, retrospective or single-center designs, heterogeneous formulas, variable outcome measures, and insufficient safety and herb-drug interaction assessment. Future research should focus on well-designed prospective studies, standardized syndrome differentiation and treatment protocols, reproducible quality-control systems, clinically meaningful endpoints, and rigorous safety evaluation. With stronger evidence and clearer translational standards, TCM may be more appropriately evaluated and integrated as a complementary component of modern gastric cancer management, rather than as a substitute for established oncological treatment.

Funding Statement

Heilongjiang Province’s Provincial Higher Education Institutions’ Central Support for Local University Reform and Development (High-level Talent Project) (2020GSP07); Heilongjiang Provincial Traditional Chinese Medicine Research Project (GY2022-05); Provincial-Level Renowned TCM Practitioner Expert Inheritance Studio Project.

Data Sharing Statement

Research data supporting this publication are available from PubMed and the CNKI repository.

Disclosure

The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.