Tumor-associated Fungi in Determining Survival of Lung Cancer Patients
Authors: Poddar Megha , Dan Sangita , Dey Sparsha , Mukherjee Meghna , Sett Soma , Mandal Subhranshu , Sengupta Sankar , Mandal Chandan 
Published: February 2025

Abstract
Fungal infections have been found to be significant causes of carcinogenesis and cancer formation. The interplay between fungal pathogens and the host immune system creates a complex environment that can facilitate the development and progression of fatal diseases. There are several mechanisms behind the role of fungi in cancer. Chronic inflammation resulting from persistent fungal infection can lead to persistent cellular damage and a pro-tumorigenic environment. Fungi such as Aspergillus, Candida, and Fusarium produce mycotoxins, which are known carcinogens that can directly cause DNA damage, mutations, and chromosomal instability. Furthermore, these mycotoxins can disrupt cellular signaling pathways and inhibit apoptosis, thereby promoting tumor survival and proliferation. Another important factor in the development of fungal-associated cancer is immunosuppression. Many fungal infections weaken the immune system, reducing its ability to recognize and eliminate malignant cells. This immunosuppressive effect is particularly pronounced in immunocompromised people. People suffering from HIV/AIDS, undergoing chemotherapy, or receiving organ transplants are at higher risk of fungal infections and the subsequent development of cancer. In addition, fungi can alter the host microbiome, leading to dysbiosis and an environment that promotes oncogenesis. The altered microbiome can impair metabolic processes and immune function, contributing to cancer progression. Some fungi can also have direct oncogenic properties, converting normal cells into malignant cells. For instance, certain fungal species, such as Malassezia, have been connected to pancreatic cancer, whereas other fungal species have been connected to esophageal and oral cancers. These relationships underscore the need for a comprehensive understanding of the fungal species involved, their metabolism, and their interactions with the host. Fungal pathogens armed with virulence factors and toxins can cause significant damage to host cells, trigger chronic inflammation, and weaken the immune system. These multifaceted processes create a favorable environment for tumor development and progression. In particular, aflatoxins, a group of fungal-derived carcinogens, have been specifically linked to hepatocellular carcinoma, a common form of liver cancer. The impact of fungal infections on cancer development extends beyond hepatocellular carcinoma. Studies have provided strong evidence for the involvement of fungi in the pathogenesis of other malignancies, including esophageal, gastric, colon, lung, cervical, skin, and ovarian cancers. It has been found that fungal infections promote cancer development by having deleterious effects on tumor immunity, promoting chronic inflammation, and interfering with the host immune response. The identification of fungal infections as potential drivers of cancer development highlights the importance of early detection, prevention, and treatment strategies targeting these infections. Antifungal therapy, along with traditional cancer treatments, can provide a dual approach to managing cancer risk and progression. Future research should focus on the molecular pathways involved in fungal-induced carcinogenesis, the role of the immune system in this process, and the development of novel therapeutics to reduce the oncogenic potential of fungal infections. Understanding these mechanisms is important to develop effective strategies to reduce the cancer burden associated with fungal infections.