HUMAN PAPILLOMAVIRUSES: FROM INFECTIOUS ENTRY TO MALIGNANCY
ICGEB Director-General, Lawrence Banks will present the studies that are being conducted at ICGEB, Italy using genome editing to identify novel therapeutics to specifically block cervical cancer growth and invasion
Human Papillomaviruses (HPVs) are major causes of human cancer, and account for over 600,000 cancer cases each year around the world. By far the most important of these is cervical cancer, which is caused by infection with a small group of so called high-risk HPV types, of which HPV16 and HPV18 are the most important. Normally these viruses infect mucosal skin and lead to largely clinically mild infections, resulting in the production of new infectious virus particles. However, under certain circumstances this normal infection process is perturbed, and changes can initiate which ultimately lead to the development of cervical cancer. The ICGEB Tumour Virology laboratory has a long standing interest in understanding how the virus enters the host cell, and then ultimately what are the mechanisms underlying the development of the cancer.
We have found that two viral oncoproteins, E6 and E7 are responsible for HPV induced malignancy. These two proteins target many cellular pathways that are essential for maintaining control of cell proliferation. In a normal virus infection, overriding these controls aids viral replication and the production of new infectious virus particles. However, overriding these controls can also lead to tumour development and cancer. Using genome editing approaches we have been dissecting the functions of E6 and E7 in cells derived from cervical cancers. Genome editing allows us to mutate specific functions of E6 and E7, and by doing so we have identified critical activities, which offer therapeutic potential. This has very important implications for future cancer therapies, as a number of compounds targeting these activities are already showing promise in other clinical trials. There is now compelling evidence for also considering these in the treatment of cervical cancer.
The conference will provide an opportunity to gauge the global incidence of new cervical cancer cases and mortality, how it develops, the persistence of infection and its importance for tumour formation. Furthermore questions regarding advocating vaccinations and the therapeutic potential of this work for cervical cancer can be developed.
Publication: Basukala, O., Mittal, S., Massimi, P., Bestagno, M. Banks, L. 2019. PLOS Pathogens The HPV-18 E7 CKII phosphor acceptor site is required for maintaining the transformed phenotype of cervical tumour-derived cells
Press contact: Suzanne Kerbavcic, ICGEB Communications, Public Information and Outreach
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