A growing body of evidence has indicated that the microbiome within the gut and tumours significantly influences cancer initiation, progression and treatment response.
However, current research primarily focuses on bacteria, whilst the role of fungi is only now starting to garner attention.
In a study published in the Science Partner journal, Research, a team of researchers from the Science and Technology Publishing House addressed the key questions that have caused confusion and hindered clinical translation.
These include the following:
- Why should we value the role of the mycobiome in oncological research?
- What will the relationship between fungi and bacteria be in cancer progression?
- How will the fungi impact cancer?
- Can we target fungi for the development of intervention strategies in anticancer treatment?
- Will the effort and investment pay back in mycobiome-driven cancer research?
Current research progress
Despite their low abundance in tumour tissues (approximately four per cent to 13.3 per cent), fungi exhibit widespread distribution, high signal activity and type-specificity across multiple cancers, including lung, breast, colorectal and pancreatic cancers.
Through highly sensitive techniques such as ITS sequencing and single-cell sequencing, tumour-associated fungi, including Candida, Malassezia and Aspergillus, have been identified.
These fungi may promote tumour progression by activating immunosuppressive pathways (e.g., Dectin-1/CARD9, IL-1β/MDSC axis) or secreting carcinogens (e.g., aflatoxins).
Concurrently, fungi and bacteria exhibit synergistic or antagonistic interactions within the microbiome, influencing the immune micro-environment and therapeutic response.
Modulating the fungal microbiome (e.g. via antifungal agents, heat-killed fungi, or combined immunotherapy) may enhance antitumour immunity.
Preliminary validation of this therapeutic potential has emerged from certain preclinical and clinical trials (e.g., itraconazole, ketoconazole).
Future prospects
The researchers predict that future fungal cancer research will progress from correlation towards causation, utilising single-cell sequencing and spatial omics to identify pro- or anti-cancer fungi, while integrating multi-kingdom interaction maps encompassing bacteria, viruses and archaea.
Technologically, standardised protocols for ITS, 18S and metagenomic sequencing will be established, alongside developing fungal enrichment sequencing and multi-omics AI models, culminating in a tumour fungal ecosystem database.
Clinically, fungal-bacterial combined biomarkers will be promoted for early screening, prognosis and immunotherapy response prediction.
Repurposed antifungal drugs such as itraconazole and ketoconazole will be utilised, alongside developing low-toxicity nanoformulations and fungal metabolite adjuvants.
Research will explore faecal fungal transplantation, attenuated engineered fungi and personalised ‘fungal prescriptions’.
Industrial advancement will drive synthetic biology-engineered medicinal fungi, targeted delivery systems and mycobiome diagnostic kits.
Societal efforts must overcome the bias of ‘prioritising bacteria over fungi’ by establishing interdisciplinary fungal-cancer alliances.
Government investment should concurrently develop ethical frameworks, antimicrobial resistance surveillance and toxicity assessment protocols.
Ultimately, this will realise mycobiome-driven precision diagnostics and therapeutics, benefiting cancer patients.