Complex Interrelationships Between Tumors, the Mycobiota, and Systemic Chemotherapy

The fungal microbiome is an increasingly recognized component of the tumor microenvironment, yet its interactions with cancer development and systemic anticancer therapy remain poorly characterized. This review summarizes current evidence on the role of fungi in tumors and their interactions with systemic chemotherapy and antifungal therapy. We discuss potential mechanisms by which the mycobiota may contribute to oncogenesis through immune modulation, remodeling of the tumor microenvironment, chronic inflammation, angiogenesis, and other tumor-supportive processes. We further examine evidence that several anticancer agents, including doxorubicin, cisplatin, and bleomycin, exhibit antifungal activity in vitro and may influence fungal growth, virulence-associated processes, and the selection of resistant fungal phenotypes. Conversely, fungal biofilm formation, hypoxia, and cellular stress-response mechanisms may affect susceptibility to antifungal and potentially anticancer agents. Particular attention is given to the poorly understood relationship between systemic chemotherapy and the gut mycobiome and its potential implications for intestinal dysbiosis and systemic complications. Overall, the complex and potentially bidirectional interactions between fungi, tumors, and systemic anticancer therapy warrant further investigation to determine their impact on treatment response and cancer outcomes, as well as their potential for therapeutic development.