The scientific community is exploring the relationship between fungi and cancer, revealing how these microorganisms interact with cancerous processes. Fungi can contribute to cancer development and offer potential avenues for its detection and treatment, suggesting a profound influence on human health.
Direct Cancer-Causing Fungi
Certain fungi are recognized for their direct ability to cause cancer, primarily through the production of toxic compounds known as mycotoxins. Aflatoxins, produced by Aspergillus species like Aspergillus flavus and Aspergillus parasiticus, represent a well-documented example of such carcinogens. These molds commonly grow on agricultural products such as corn, groundnuts, cereals, and other grains. Among the various aflatoxins, Aflatoxin B1 (AFB1) is considered the most potent carcinogen and has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC/WHO).
Long-term exposure to AFB1 is a significant risk factor for hepatocellular carcinoma (HCC), a type of liver cancer, particularly in regions of Africa and Asia where nearly 50% of HCC cases may be attributed to aflatoxins. When metabolized in the liver by cytochrome P450 enzymes, AFB1 forms a reactive intermediate called AFB1-8,9 epoxide (AFBO). This AFBO molecule can bind to DNA, forming adducts that lead to genetic mutations.
These DNA adducts primarily cause a guanine to thymine (G→T) transversion at codon 249 of the p53 tumor suppressor gene, which is a common mutation observed in HCC. These alterations disrupt normal cellular function, promoting uncontrolled cell growth and tumor formation. Beyond direct DNA damage, aflatoxins can also induce epigenetic changes, including DNA methylation and histone modifications, which further contribute to the development and progression of liver cancer.
Fungi’s Role in the Cancer Environment
Beyond direct causation, fungi also interact with cancer in more nuanced ways, particularly through their presence within the body’s various microbial communities, collectively known as the “mycobiome.” This includes fungi residing in the gut and those found directly within tumor tissues. These fungal populations can significantly influence the tumor microenvironment, which is the complex ecosystem surrounding cancer cells.
Fungi within the tumor microenvironment can modulate immune responses, often contributing to an immunosuppressive state that allows tumors to evade the body’s defenses. For instance, studies in pancreatic ductal adenocarcinoma (PDAC) have shown that intratumoral fungi can enhance the secretion of interleukin (IL)-33 from cancer cells. This cytokine then recruits pro-tumorigenic immune cells, such as T helper 2 (Th2) cells and innate lymphoid cells 2 (ILC2), which can inhibit anti-tumor immunity and accelerate cancer progression.
The mycobiome can also affect tumor growth and progression by altering cellular metabolism and promoting inflammation. Furthermore, the presence of fungi can impact the effectiveness of cancer treatments. The mycobiome may influence how chemotherapy drugs are metabolized or contribute to drug resistance, similar to how certain bacteria can degrade chemotherapeutic agents.
Fungi in Cancer Management
Fungi and their compounds are increasingly being investigated for their potential in cancer management, encompassing both therapeutic and diagnostic applications. Many fungal metabolites, particularly those derived from medicinal mushrooms, possess anti-cancer properties. These compounds, such as polysaccharides (e.g., β-glucan), terpenoids, and phenolic compounds, can modulate the immune system, inducing tumoricidal activity in immune cells like natural killer (NK) cells and macrophages, or directly inhibiting tumor cell growth.
Research is also exploring the use of engineered fungi as oncolytic agents, which are designed to selectively infect and destroy cancer cells while sparing healthy tissue. While still in early stages, this approach holds promise for targeted therapies. Fungi also represent a rich source for the discovery of new anti-cancer drugs, much like penicillin was derived from a fungus.
Over 60% of current anti-cancer drugs have natural product origins, and fungi are a vast, underexplored reservoir for novel compounds with diverse mechanisms of action against cancer cells. In terms of diagnostics, fungal biomarkers could offer new ways to detect cancer early or monitor treatment efficacy.
Unique fungal profiles have been observed in biopsies of certain cancers, suggesting that specific fungal species or their metabolic byproducts could serve as indicators of disease presence or progression. As scientific understanding of the fungal-cancer connection deepens, these microorganisms are becoming valuable subjects in the ongoing effort to improve cancer detection and treatment strategies.