MedicalResearch.com Interview with:
Manon Eckhardt, PhD
The Quantitative Biosciences Institute
University of California San Francisco
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Infection with Human Papillomavirus (HPV) causes 5% of all cancers worldwide, including cervical cancer and an increasing number of head and neck cancers. Most cancers are caused by mutations in genes, leading to the production of malfunctioning proteins that result in unconstrained cell division. However, certain viruses like HPV can cause cancer without introducing mutations.
In this study, we compared cancers of the same type (i.e. head and neck) that are caused by either mutation or virus infection to identify important processes that are dysregulated in both subsets. We hypothesized that identifying which proteins the virus binds can lead the way to prioritize which of the proteins and cellular processes (pathways) that are affected in cancer cells are most important. To do this, we identified the complete set of human proteins that interact with HPV. We next determined genes that were more frequently mutated in non-viral cancers, and combined both data sets. The proteins we find to be both binding to HPV and mutated in non-viral cancers will be potential targets for new, more specific drug development, and help better understand the development of head and neck cancer.
From the many pathways we identified in this study, we highlighted two pathways with further mechanistic studies: the oxidative stress response, which helps cancer cells survive, as well as a pathway that allows the cancer to spread to other parts of the body.
MedicalResearch.com: What should readers take away from your report?
Response: Cancers associated with different causes share vulnerabilities in the same overall processes. We show here that these can be identified by looking at human proteins that bind to viral proteins, and are mutated in non-virally caused cancers. This approach led us to discover that a viral protein which wasn’t previously known to play a role in cancer causes HPV-associated head and neck cancer cells to increase their ability to spread to other parts of the body.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: We can learn a lot from combining different types of data in the right way. Viruses, because they depend on cells to replicate, can serve as excellent tools to study important processes in cells. Our study revealed a number of interesting and previously underappreciated pathways impacted in HPV-associated cancers. We thus hope that this body of work will inspire substantial follow-up studies, including targeted approaches to treat HPV-related cancers. Also, the methods we developed here can be used to study other virus-associated cancers, such as liver cancer, which can be caused by infection with Hepatitis B and C Virus (HBV / HCV).
Manon Eckhardt, Wei Zhang, Andrew M Gross, John Von Dollen, Jeffrey R Johnson, Kathleen E Franks-Skiba, Danielle L Swaney, Tasha L Johnson, Gwendolyn M Jang, Priya S Shah, Toni M Brand, Jacques Archambault, Jason F. Kreisberg, Jennifer R. Grandis, Trey Ideker, Nevan J Krogan. Multiple Routes to Oncogenesis are Promoted by the Human Papillomavirus-Host Protein Network. Cancer Discovery, 2018; CD-17-1018 DOI: 10.1158/2159-8290.CD-17-1018
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