Can astragalus polysaccharides truly boost the treatment of pancreatic cancer?

Abstract

The research on astragalus polysaccharides (APS) in pancreatic cancer has garnered increasing interest due to its potential therapeutic benefits. APS, derived from the Astragalus membranaceus plant, exhibits diverse biological activities, including immune modulation and anti-tumor effects. In this study, we presented a retrospective analysis study exploring the potential benefits of combining APS with gemcitabine plus tegafur gimeracil oteracil potassium capsule (S-1) in pancreatic cancer treatment. The finding suggests that APS may enhance treatment efficacy, improve immune function, and reduce adverse reactions, offering a valuable complementary approach to standard chemotherapy. Further research is needed to validate these findings and optimize APS usage in clinical practice. This combination therapy represents a compelling avenue for improving pancreatic cancer management and may ultimately contribute to better patient outcomes.

Key Words: Astragalus polysaccharides; Pancreatic cancer; Drug combination

Core Tip: Astragalus polysaccharides combined with chemotherapy have demonstrated an enhanced efficacy and reduced toxicity in the treatment of pancreatic cancer. However, its true clinical value requires further research to be confirmed.

TO THE EDITOR

Pancreatic cancer is a highly aggressive malignancy characterized by rapid progression, subtle early symptoms, and high metastatic potential, creating significant challenges in clinical treatment[1]. To date, chemotherapy remains the main treatment for advanced pancreatic cancer, however, its effectiveness is limited, and the associated adverse effects are severe[2] In recent years, the integration of traditional Chinese medicine (TCM) into the comprehensive cancer treatment has received increasing attention[3,4]. Among them, astragalus polysaccharide (APS), an immunomodulator, has shown potential in enhancing the effectiveness of chemotherapy and reducing associated toxicity[5-7]. A retrospective study by Li et al[8], published in the World Journal of Clinical Oncology, explored the short-term efficacy and long-term survival benefits of APS combined with gemcitabine and S-1 (GS) regimen for pancreatic cancer, providing new evidence for integrative treatment with Chinese and western medicine[9].

Study highlights and clinical significance

This study included 97 patients diagnosed with stage III-IV pancreatic cancer, 41 of whom received APS combined with GS treatment, while 56 received only GS chemotherapy[8]. The analysis results demonstrated that the combination therapy group had a significantly higher objective response rate (51.22% vs 30.36%) and disease control rate (56.10% vs 35.71%) compared to the monotherapy group (P < 0.05). Consistent with the efficacy, the combination therapy group had a significant increase in the proportions of CD3⁺ and CD4⁺ T cells and the CD4⁺/CD8⁺ ratio, suggesting that APS may enhance antitumor effects by improving immune function. Moreover, the combination therapy significantly reduced the incidence of leukopenia (17.07% vs 37.50%), thrombocytopenia (9.76% vs 28.57%), and fatigue (31.71% vs 60.71%) and prolonged the median survival time (394 days vs 339 days, HR = 0.66). These results provide preliminary evidence for the auxiliary role of APS in the treatment of pancreatic cancer[7]. From a mechanistic perspective, the immunomodulatory effects of APS are likely attributed to its ability to activate dendritic cells (DCs), promote T cell proliferation, and modulate cytokine (e.g., IL-2) secretion[10,11]. Also, previous studies have shown that APS can reverse the immunosuppressive tumor microenvironment through mechanisms such as inhibiting PD-L1 expression and regulating the TLR4/MyD88 signaling pathway[12,13]. This study further validated the immune-enhancing effect of APS in clinical practice, providing a rationale for its combination with chemotherapy in cancer treatment[14].

Methodological evaluation and limitations

As a retrospective study, this research has some limitations. First, selection bias may existed[15], since patients in the combination therapy group may have been selected due to better physical conditions or higher acceptance of TCM, and the retrospective design cannot fully control for confounding factors (such as baseline patient characteristics, comorbidities, etc.)[16,17]. Although the authors report no statistical differences in baseline characteristics between the two groups, the small sample size (n = 97) may restrict the robustness of the conclusions[18]. Second, the study did not specify whether the efficacy assessment was conducted through a blinded evaluation of imaging. The absence of blinding could introduce subjective bias[19]. In addition, the specific dosage, treatment duration, and standardized production process of APS were not detailed, which reduces the reproducibility of the results. It is worth noting that the study did not explore the specific molecular targets or mechanisms of action of APS but rather inferring its effects indirectly through peripheral blood immune markers. Future studies should incorporate basic experiments (such as animal models and cell experiments) to further explore the synergistic mechanism of APS with chemotherapies[20-22].

Implications for clinical practice

Despite of these limitations, this study provides a new approach for the comprehensive treatment of pancreatic cancer[23]. For patients with advanced cancer who are not suitable for surgery, APS combined with chemotherapy may offer a safe and effective option, especially in improving quality of life and prolonging survival[24,25]. Individualized dosing should be carefully considered when clinicians incorporating APS into chemotherapy regimens, ensuring that immune markers and potential adverse reactions are closely monitored[26].

Future research directions

Increasing sample size and prospective design: Conducting large-scale, multicenter randomized controlled trials are essential to validate the reliability of the current findings, as well as the optimal dosage and treatment duration of APS[27].

Mechanistic exploration: Advanced omics technologies (such as single-cell sequencing and proteomics) should be employed to further determine the specific pathways through which APS modulates the tumor microenvironment, including its effects on Treg cells and DC subpopulations[28].

Standardization and quality control: Given the complex composition of TCMs, it is essential to establish standardized production processes and quality control systems for APS to ensure the comparability of study results[29].

Combination with other therapies: Investigating the combination of APS with immune checkpoint inhibitors or targeted therapies may further break through the treatment bottleneck of pancreatic cancer[11].

CONCLUSION

The study by Li et al[8] preliminary proved the clinical values of APS combined with the GS regimen in pancreatic cancer treatment. With its enhanced immune function and reduced toxicity, it provides a scientific support for integrative Chinese and Western medicine[30]. However, these results should be interpreted with caution due to the inherent limitations of the retrospective design and the absence of mechanistic investigations. In the future, with more rigorous study designs and interdisciplinary collaboration, we expected to translate APS from the laboratory to clinical application, ultimately benefiting more pancreatic cancer patients[31].

ACKNOWLEDGEMENTS

The authors would like to thank Mrs Xichen Wang (MSD China, Shanghai, China) for providing academic information consulting support. The authors would also like to express their gratitude to Professor Kaiyan Liu (Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou, China) for her editing and proofreading of the manuscript.