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<p>Gastrointestinal (GI) cancers remain a leading cause of cancer mortality worldwide, and many patients with advanced disease continue to respond poorly to standard therapies. Although immune checkpoint inhibitors have transformed the management of several solid tumors, their benefits in most GI cancers are limited by low tumor mutational burden, microsatellite stability, and immunologically “cold” tumor microenvironments. These limitations have stimulated interest in safe, biologically active adjuvants capable of enhancing antitumor immunity. Ginsenosides, the principal bioactive components of ginseng, exhibit diverse anticancer and immunomodulatory properties that may help overcome resistance to immunotherapy. Preclinical studies in liver, colorectal, gastric, and esophageal cancer models demonstrate that selected ginsenosides promote apoptosis, influence DNA damage responses, inhibit angiogenesis, modulate inflammatory signaling, and downregulate PD-L1 and other immune resistance pathways. Advanced formulations, including ginseng-derived nanoparticles and liposomal systems, further suggest potential roles in drug delivery and tumor microenvironment remodeling. Clinical evidence from traditional Chinese medicine also indicates that ginseng-based preparations can support immune function, mitigate treatment-related fatigue, and improve tolerance to chemo-radiotherapy. However, the precise molecular targets, optimal combinatorial strategies, and predictive biomarkers for ginsenoside-mediated immunomodulation remain insufficiently defined. Integrating systems pharmacology, single-cell technologies, and modern clinical trial design will be essential to establish the therapeutic value of ginsenosides as adjuvants to immunotherapy in GI cancers.</p> Graphical abstract <p></p>

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Enhancing immune checkpoint inhibitor response in gastrointestinal cancers through ginsenoside based adjuvant therapy

  • 期刊论文

  • 发表日期：

    2026年6月18日

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  • Hamzeh J. Al-Ameer,
  • Omayma Salim Waleed,
  • S. Renuka Jyothi,
  • Priya Priyadarshini Nayak,
  • Siya Singla,
  • Gurjant Singh,
  • Annaev Umidjon,
  • Azizjanov Khushnud Maksudovich,
  • Manoj Kumar-Mishra

摘要

Gastrointestinal (GI) cancers remain a leading cause of cancer mortality worldwide, and many patients with advanced disease continue to respond poorly to standard therapies. Although immune checkpoint inhibitors have transformed the management of several solid tumors, their benefits in most GI cancers are limited by low tumor mutational burden, microsatellite stability, and immunologically “cold” tumor microenvironments. These limitations have stimulated interest in safe, biologically active adjuvants capable of enhancing antitumor immunity. Ginsenosides, the principal bioactive components of ginseng, exhibit diverse anticancer and immunomodulatory properties that may help overcome resistance to immunotherapy. Preclinical studies in liver, colorectal, gastric, and esophageal cancer models demonstrate that selected ginsenosides promote apoptosis, influence DNA damage responses, inhibit angiogenesis, modulate inflammatory signaling, and downregulate PD-L1 and other immune resistance pathways. Advanced formulations, including ginseng-derived nanoparticles and liposomal systems, further suggest potential roles in drug delivery and tumor microenvironment remodeling. Clinical evidence from traditional Chinese medicine also indicates that ginseng-based preparations can support immune function, mitigate treatment-related fatigue, and improve tolerance to chemo-radiotherapy. However, the precise molecular targets, optimal combinatorial strategies, and predictive biomarkers for ginsenoside-mediated immunomodulation remain insufficiently defined. Integrating systems pharmacology, single-cell technologies, and modern clinical trial design will be essential to establish the therapeutic value of ginsenosides as adjuvants to immunotherapy in GI cancers.

Graphical abstract