Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound

Area of Science:

• Biomedical research
• Cancer biology
• Pharmacology

Background:

• Hepatocellular carcinoma, oral, and colorectal cancers cause significant mortality in Taiwan.
• Circulating tumor cells (CTCs) are crucial for cancer progression and metastasis.
• Developing novel therapeutic strategies targeting CTCs is essential for improving patient outcomes.

Purpose of the Study:

• To develop a circulating tumor cell (CTC) organoid culture workflow for testing Antrodia cinnamomea mycelium (ACM)-derived compounds.
• To evaluate the chemosensitization potential of ACM-derived bioactive compounds, particularly GKB202, in patient-derived tumors.
• To assess the safety and pharmacokinetic profile of GKB202 in preclinical models.

Main Methods:

• Established a CTC organoid culture system from patient samples.
• Screened three ACM-derived bioactive compounds for anti-cancer activity.
• Investigated the synergistic effects of GKB202 with 5-fluorouracil (5-FU) on 8 different patient-derived tumors.
• Conducted acute toxicity and hepatic metabolism studies of GKB202 in rats.

Main Results:

• GKB202 demonstrated significant and consistent cytotoxic and 5-FU sensitizing effects across 8 patient-derived tumors.
• GKB202 was well-tolerated in rats up to 20 mg/kg, with rapid liver clearance.
• Liquid fermentation of ACM yielded bioactive compounds effective in controlling CTCs, especially in combination with 5-FU.

Conclusions:

• ACM-derived GKB202 exhibits potent chemosensitizing properties against various patient-derived tumors.
• GKB202 shows a favorable safety profile in preclinical studies, suggesting its therapeutic potential.
• GKB202 warrants further clinical investigation as a potential adjunct to 5-FU-based combination therapy for cancer treatment.