ParVirCancer-Network

The liver flukes O. viverrini and C. sinensis remain a major heath burden throughout eastern Asia. They are recognized as group I carcinogens by the International Agency for Research on Cancer (IARC). Long-term infections lead to Cholangiocarcinoma (CCA), a bile-duct cancer with very poor prognosis. Liver flukes release proteins that exacerbate cancer development, but the proximate mechanisms responsible for cells malignant transformation remain unknown. We have identified viruses associated with these liver flukes and showed that some of these are excreted by parasites. Here, we propose to investigate the role of these viruses in cancer, which may lead to new treatments or preventive therapies for CCA. Our central hypothesis is that viruses of liver flukes can impact host health by modulating host immune response, infecting host cells, and modulating the excretion of parasite virulence factors. We aim to obtain funding from the US National Institutes of Health (NIH) involving the National Cancer Institute (NCI) in response to the funding opportunity announcement (FOA) PAR-23-055 Co-infection and Cancer (R01). This FOA aims to enhance epidemiological and mechanistic investigations focusing on micro- and macro-organisms co-infections with a known oncogenic agent to determine how they contribute to carcinogenesis and identify novel opportunities for prevention and treatment. ParVirCancer involves four partners that have been involved for decades in the study of infectious diseases and public health. All collaborators are leaders in their field with substantial track record and demonstrate complementary expertise - in virology at Institut Pasteur Paris - in liver flukes CCA at Khon Kaen University - in molecular parasitology at George Washington University -, and in proteomics of parasite excretory secretory vesicles at James Cook University. The scientific excellence of the partners, access to biological samples, availability and already developed protocols and access to Biological Safety laboratory and animal experiment infrastructures needed for the project makes them uniquely situated and qualified to conduct this project and develop follow-up therapeutic and preventive applications.