Potential for Medicinal Mushroom Extracts as an Adjunctive Treatment to Enhance Conversion Therapy in Colorectal Cancer with Liver and Peritoneal Involvement

Colorectal cancer (CRC) with liver metastases (LM) and peritoneal metastases (PM) presents a formidable challenge, with poor prognosis despite advances in systemic chemotherapy and combined surgical approaches like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Median overall survival (OS) for unresactable cases ranges from 12–24 months with modern regimens (e.g., FOLFOX/FOLFIRI + targeted therapies), yet conversion to resectable disease remains limited by disease extent and treatment toxicity. This paper proposes that medicinal mushroom extracts, particularly polysaccharopeptides (e.g., PSK and PSP) from Trametes versicolor and bioactive compounds from species like Ganoderma lucidum, could enhance conversion therapy outcomes in CRC with LM and PM. Evidence from preclinical and clinical studies demonstrates that these extracts exert anticancer effects through multiple mechanisms, including suppression of multidrug resistance, immune checkpoint blockade (e.g., PD-1/PD-L1), regulation of oncogenic signaling pathways (e.g., PI3K/AKT, MAPK, NF-κB), and robust immunomodulation. Clinical trials, including meta-analyses of over 8,000 patients, report improved survival and tolerability when combined with chemotherapy, primarily in postoperative settings. Our own meta-analysis involving a total of 2397 patients finds a 10% relative increase in the probability of survival at 5 years compared to the reference group, with a survival risk ratio (RR) of 1.10 (95% CI: 1.04–1.15). The author hypothesizes that integrating these extracts into preoperative regimens could enhance the efficacy of chemotherapy, increase surgical eligibility (e.g., R0 resection rates), and mitigate toxicity, potentially extending OS beyond current benchmarks (e.g., 26–48 months with CRS-HIPEC). While direct evidence in unresectable CRC with dual metastases is lacking, the biological plausibility and safety profile of mushroom extracts warrant prospective trials to validate their role in conversion therapy.