The dual role of Ganoderma lucidum polysaccharides in cancer treatment: Meridian tropism-based direct inhibition and immune-mediated modulation.

Ganoderma lucidum, a highly valued medicinal mushroom in Traditional Chinese Medicine (TCM), has a long history of clinical use. Although its immunomodulatory and anticancer properties have been extensively investigated, an integrated framework connecting traditional therapeutic principles with modern molecular pharmacology remains underdeveloped. This review proposes a novel meridian-based pharmacological framework that bridges classical TCM theory with contemporary precision oncology. Specifically, the direct tumor-suppressive effects of G. lucidum polysaccharides (GLPs) across organ-specific malignancies, including lung, liver, hematological, and genitourinary cancers, are systematically examined to explore potential associations between classical meridian tropism and tissue-specific anticancer activity. These organ-targeted effects are further linked to experimentally validated mechanisms, including cell-cycle arrest, apoptosis induction, DNA repair interference, autophagy modulation, inhibition of epithelial-mesenchymal transition, and sensitization to chemotherapy. Beyond their direct tumor-suppressive effects, GLPs also exhibit potent immunomodulatory activities that may enhance cancer immunotherapy. Their roles in regulating systemic immunity and remodeling the tumor microenvironment are highlighted through macrophage reprogramming, dendritic cell maturation, and cytotoxic T-cell activation, together with their potential synergistic interactions with immune checkpoint blockade therapies. By integrating direct tumor suppression with immune-mediated mechanisms within a meridian-based framework, this review provides a comprehensive perspective on the therapeutic potential of GLPs and offers insights to support their future clinical translation in oncology.