Project description
Studying the mechanisms of Epstein-Barr virus-associated cancer
The Epstein-Barr virus (EBV) is responsible for around 200 000 new cancer cases annually. A potentially effective way to treat people with EBV-associated cancers is with small-molecule inhibitors targeting viral proteins. However, no such drugs exist. Recent scientific data suggest that the EBV-encoded BILF1, a constitutively active G-protein coupled receptor, could further the development of anti-viral drugs to treat EBV-related tumours. The EU-funded VirGO project aims to explore the role of BILF1 in germinal centre B-cell transformation and identify how BILF1 contributes to the established phenotype of Burkitt lymphoma cells. It will also link these phenotypes to primary tumour pathological features and to patient response to therapy. The project will provide further insight into EBV-mediated oncogenesis mechanisms.
Objective
The Epstein–Barr virus (EBV) is widespread in all human communities. While most people carry EBV as a life-long asymptomatic infection, in some people, EBV contributes to malignant transformation and is responsible for ~200,000 new cancer cases/year. Small molecule inhibitors targeting viral proteins could be an effective option to treat people with EBV-associated cancers. However, no such drugs exists which in part reflects the limited repertoire of targetable virus proteins present in EBV-driven cancers. Recently, the Experienced Researcher (ER) has shown that the tumour cells of EBV-associated cancers such as Burkitt lymphoma (BL), express the EBV-encoded BILF1, a constitutively active G-protein coupled receptor (GPCR). Furthermore, preliminary data by the ER indicate that BILF1 partially recapitulates the aberrant transcriptional programme of BL and is likely to do so through activation of oncogenic cell signalling pathways that include AKT-mTOR. These data suggest that BILF1 could be a realistic therapeutic target, raising the possibility of advancing the development of anti-viral drugs to treat EBV-related tumours; GPCRs are the most successful class of drug target for the treatment of human disorders and are emerging as anti-cancer targets. In this project the ER will harness new models of B cell lymphomagenesis available in the host laboratory to: 1) Explore the role of BILF1in the transformation of germinal centre B cells; the progenitors of BL; 2) Identify how BILF1 contributes to the established phenotype of BL cells; and 3) Link these phenotypes to pathological features of the primary tumour and to patient response to therapy. Thus, the Fellowship will significantly advance knowledge of the mechanisms of EBV-mediated oncogenesis, in turn paving the way for the development of new EBV-targeted small molecule drugs. The ER will emerge from this project with a new advanced skill-set and the capability to launch her own high level scientific research.
Fields of science
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
- Limerick
Ireland