Ganodermanontriol and Lanostane Triterpenoid Derivatives in Cancer Cell Biology: Signaling Network Modulation, Cell‐Cycle Control and Tumor Microenvironment Reprogramming

Ganodermanontriol (GDNT), a lanostane-type triterpenoid derived from Ganoderma lucidum, exhibits multiple pharmacological properties, with emerging evidence supporting its anticancer potential. Despite the long-standing medicinal use of G. lucidum, the specific role and mechanisms of GDNT in oncology require further clarification. This review presents a comprehensive analysis of preclinical studies investigating the anticancer activity of GDNT in various cancer types, including nasopharyngeal, hepatocellular, gastric, colorectal, breast, prostate, and lung malignancies. Relevant experimental literature was identified and evaluated, with emphasis on in vitro and in vivo models exploring the molecular mechanisms of GDNT. Key pathways implicated in its activity include NF-κB/MAPK, TLR4/MyD88, Wnt/β-catenin, CES2/MPA metabolism, and androgen receptor signaling. Experimental findings demonstrate that GDNT induces apoptosis, arrests cell cycle progression, and inhibits tumor cell proliferation, migration, and invasion. It also modulates the tumor microenvironment through suppression of M2 macrophage polarization and pro-tumor cytokine expression. Semi-synthetic analogs of GDNT display improved cytotoxicity and selectivity, highlighting the relevance of structural optimization in enhancing bioactivity. Although clinical data on GDNT are currently lacking, studies involving G. lucidum extracts suggest potential benefits as supportive agents in oncologic care, particularly in immune modulation and enhancement of chemotherapeutic efficacy. Ongoing research into GDNT's pharmacological profile, including its derivatives, may support its development as a novel candidate in cancer therapeutics.