Characterizing the Mechanistic Insights and Clinical Relevance of Fusobacterium in Tongue Cancer
Implementing Organization
Tata Memorial Centre (Hospital), Maharashtra
Principal Investigator
Dr. Amit Dutt
Tata Memorial Centre (Hospital), Maharashtra
CO-Principal Investigator
Prof. sudhir V Nair
Tata Memorial Centre (Hospital), Mumbai, Maharashtra-400012
CO-Principal Investigator
Dr. Anirban Banerjee
Indian Institute of Technology (IIT)
CO-Principal Investigator
Prof. Tapasya srivastava
University of Delhi
About
The Human Microbiome Project has identified 48 microbial habitats in the human body, maintaining balanced symbiotic/commensal relationships. A shift in this balance, known as a 'dysbiosis', can lead to disease, with chronic inflammation often linked to cancer initiation and progression. The role of the microbiome in human cancer has become a focus of research. A recent study identified a significant prevalence of Fusobacterium in tongue cancer samples, similar to its occurrence in colorectal tumors. Fusobacterium is mutually exclusive to HPV infection and is characterized by overexpression of miRNAs associated with inflammation, elevated innate immune cell fraction, and nodal metastases. The study proposes to extend the findings by examining the functional validity and relevance of the Fusobacterium/tongue cancer association, the influence of Fusobacterium on tongue cancer growth, and the effect of Fusobacterium on the immune microenvironment. This will involve studying the impact of the bacterial infection on the proliferation, invasion, migration, and other characteristics of tongue tumor cells. The study will also identify host-induced molecular correlates in tongue cancer cells in response to Fusobacterium infection. Lastly, the study plans to establish a tongue cancer orthotopic mouse model and develop the first patient-derived-xenograft (PDX) model and PDX-derived primograft cultures in tongue cancer. This will investigate the clinical utility of Metronidazole, a broad spectrum microbial inhibitor, in impeding the growth of tongue tumors in PDX mice model and PDX-derive primograft cellular culture.