Fungal Compounds Show Promise in Cancer Therapy: Mechanisms, Molecules, and Future Outlook

A new review published in AIMS Molecular Science (2025) offers one of the most detailed inventories yet of fungal compounds with anticancer potential. With cancer incidence expected to rise nearly 77% by 2050, the search for more effective, less toxic treatments is more urgent than ever. Mushrooms and endophytic fungi are emerging as promising sources of pharmacologically active molecules that interact with key cancer-related pathways.

Image credits: Sora

Mushrooms in Traditional Medicine and Modern Diets

Mushrooms have long been part of traditional medical systems in Asia, notably in China, Japan, and India. Ganoderma lucidum, Lentinula edodes, and Cordyceps sinensis are valued not just for their culinary use but for their therapeutic compounds. Rich in β-glucans, essential amino acids, and minerals, these species also contribute to immune support and antioxidant defence.

Key Bioactive Fungal Compounds

The review highlights a wide range of fungal metabolites with anticancer activity:

• Cordycepin (from Cordyceps militaris): Inhibits metastasis and induces apoptosis in breast and lung cancers.

• Ganoderic acids (from Ganoderma lucidum): Suppress proliferation in prostate and pancreatic cancer by modulating Wnt and STAT3 signalling.

• Camptothecin (from endophytic fungi): A precursor to irinotecan, widely used in colorectal cancer.

• Taxol (paclitaxel): Traditionally extracted from yew trees, now also produced by endophytic fungi like Taxomyces andreanae.

• Other actives include fumagillin, resveratrol, and ergot alkaloids, each with mechanisms related to DNA repair inhibition or anti-angiogenesis.

  
  

Molecular Mechanisms of Action

Fungal compounds influence cancer development through several pathways:

• Apoptosis induction via mitochondrial disruption and death receptor signalling

• Cell cycle arrest at G0/G1 or G2/M phases

• Anti-angiogenesis by downregulating VEGF and related signals

• Anti-metastasis through suppression of MMP enzymes and adhesion molecules

• Immunomodulation, especially β-glucans activating macrophages and cytokine cascades

  
  

Synergies with Chemotherapy

Several studies in the review explore how fungal extracts can complement standard treatments:

• Pleurotus pulmonarius enhanced the efficacy of cisplatin in preclinical models

• Ganoderma spore extracts reduced resistance to trastuzumab in HER2+ breast cancer

• Patients receiving fungal adjuncts often showed improved immune profiles and reduced chemotherapy toxicity

  
  

Biotechnological Applications and Sourcing

Endophytic fungi offer a sustainable alternative for producing complex plant-derived anticancer agents. Advances in fermentation, gene cloning, and biosynthetic pathway analysis are making it possible to scale production of compounds like camptothecin and taxol from microbial sources rather than depleting endangered plant species.

Safety, Toxicity, and Clinical Limitations

While many compounds are safe at therapeutic doses, the review cautions against generalising fungal safety. Some species, such as Amanita and Galerina, contain potent hepatotoxins. Others, like orellanine from Cortinarius spp., show renal toxicity.

Only a handful of these compounds have reached large-scale clinical trials. Further work is needed to standardise extraction methods, define therapeutic windows, and understand long-term effects.

Outlook

Fungi represent a largely untapped reservoir of potential anticancer agents. Their diverse mechanisms of action and ability to synergise with existing therapies position them as key candidates in the next generation of cancer treatment strategies. Continued interdisciplinary research will be essential to translate this promise into clinical benefit.

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Citation

Roy M, Paul C, Pal N, Saha T, Das N. (2025). Pharmacological and therapeutic inventory of fungi in cancer therapy—A comprehensive review. AIMS Molecular Science, 12(1): 67–98. https://doi.org/10.3934/molsci.2025005