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

Abstract

Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test Antrodia Cinnamomea mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of Antrodia cinnamomea mycelium (ACM) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.

Identification of Common Liver Metabolites of the Natural Bioactive Compound Erinacine A, Purified from Hericium erinaceus Mycelium

“…This result is reasonable, judging from t 1/2 values, because rat liver has been reported to metabolize faster than human liver [28]. Compared with other compound reports using rat liver S9, GKB202 of the Antrodia cinnamomea mycelium (t 1/2 = 3.68 min) was metabolized more rapidly than erinacine A [29]. The previous report showed that there was no-observed-adverse-effect of 3 g/kg body weight/day erinacine A-enriched HE in 28-day oral feeding in Sprague-Dawley rats.…”

Application of Drug Testing Platforms in Circulating Tumor Cells and Validation of a Patient-Derived Xenograft Mouse Model in Patient with Primary Intracranial Ependymomas with Extraneural Metastases

“…The clinical application of circulating tumor cells has many purposes, including as therapeutic targets for metastatic tumors, early diagnosis, prognosis prediction, and real-time molecular phenotyping and minimal invasive liquid biopsies [ 31 ]. Furthermore, CTCs serve as a drug testing platform provided by living cells [ 32 ], and a correlation between CTC drug sensitivity profiles and the treatment response has been demonstrated in patients with pancreatic duct adenocarcinoma [ 17 ]. Recently, the application of CTCs to brain tumor treatment has been associated with great concern and has been evaluated.…”

Tumor organoids: applications in cancer modeling and potentials in precision medicine

“…Combination treatment with talazoparib (a PARP inhibitor) and CX-5461 (an inhibitor of RNA polymerase I transcription and an activator of the DNA damage response) might be a promising candidate treatment for HR-proficient patients who are not suitable for PARP inhibitor monotherapy, which was verified by increased DNA damage and decreased growth of organoids derived from HR-proficient castrate-resistant PC after treatment [177]. Based on tumoroids generated from circulating tumor cells of patients with HCC, oral cancer, or CRC, the Antrodia cinnamomea mycelium-derived bioactive compound GKB202 was indicated to be a promising adjuvant and enhancer for 5-FU-based treatment [178]. Collectively, organoids might serve as an excellent platform to explore novel and promising combination treatment strategies for patients with intractable tumor types.…”