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Massey researcher awarded $465,000 to investigate HPV, head and neck cancers

VCU Massey Cancer Center researcher Larisa Litovchick, M.D., Ph.D., was recently awarded $465,000 from the National Institute of Dental and Cranial Research to further investigate how human papillomavirus (HPV) leads to head and neck cancers. Findings may aid the development of novel targeted treatments.

The incidence rate of HPV-positive oral cancers is steadily increasing worldwide,” said Litovchick, a member of Massey’s Cancer Molecular Genetics research program and associate professor in the Department of Internal Medicine at the VCU School of Medicine. “In order to improve the prevention and treatment of this disease, we must better understand the early steps of HPV tumor pathogenesis – the biological mechanisms by which tumors form – in the oral cavity.” 

According to the Centers for Disease Control and Prevention, HPV-related oropharyngeal cancers represent up to 70 percent of all oropharyngeal cancers, and HPV16 is responsible for 90 percent of these cases. While the HPV vaccine may curb future incidences, there is an urgent need to study HPV16 cancer pathogenesis to reduce the risk of cancer among populations currently infected with the virus. 

“In HPV-positive cancers, two oncogenic proteins, E6 and E7, play essential roles in cancer cell proliferation and survival,” said Litovchick. “We will use our novel mouse genetic models to understand the mechanisms used by viral proteins E6 and E7 for inactivating the host tumor suppressor mechanisms during early steps of HPV cancer pathogenesis.” 

Iain Morgan, Ph.D., director of the VCU Philips Institute for Oral Health Research, chair of the VCU Division of Oral and Craniofacial Molecular Biology and a member of Massey’s Cancer Molecular Genetics research program, will serve as a co-primary investigator on the project. 

“Oncogenic types of HPV cause five percent of all cancers, including a subset of head and neck cancer,” said Morgan. “They also cause a number of other cancers, including cervical, anal, penile and vulvar. Our findings will increase our understanding of these HPV-positive cancers.”

Litovchick and Morgan collaborated with Jolene Windle, Ph.D., resource director of Massey’s Transgenic/Knock-out Mouse Shared Resource and co-leader of Massey’s Cancer Molecular Genetics research program, to develop two novel mouse genetic models by mutating one of the components of the dimerization partner, RB-like, E2F and MuvB (DREAM) protein complex, which is responsible for the regulation of cell cycle-dependent gene expression. They will cross the E6 or E7 mice with models to determine the effect of these mutations on the animal susceptibility to the HPV tumorigenesis (tumor formation). 

“This is a first of its kind study and it will reveal the currently unknown role of DREAM in HPV-driven cancers,” said Morgan.

This research builds upon years of work conducted by Litovchick on the function and regulation of the DREAM protein complex and Morgan’s work on understanding HPV interaction with the host cell. 

“In the future, we are interested in using our new animal models to better understand the response of HPV-positive and HPV-negative oral cancers to radiation therapy,” said Litovchick. “Clinical evidence suggests that HPV-positive tumors are more sensitive to this treatment but the underlying mechanisms for this difference are not well understood. It is possible that deregulation of the DREAM complex by E6 and E7 could play a role in this effect.” 

Preliminary research for this study was supported in part by a Massey Cancer Center multi-PI award shared by Litovchick and Morgan, as well as by Massey start-up funding – all funding made possible by generous philanthropic donations. 

“We anticipate our findings will enhance the understanding of how HPV causes cancer,” said Litovchick. “This knowledge is required for the identification of new therapeutic targets that we can develop to treat HPV-positive cancers.”

To learn more about how you can support new ideas and promising research at VCU Massey Cancer Center, contact Massey’s Office of Development at (804) 828-1450.

 

Written by: Melissa Mitchell

Posted on: September 9, 2020

Category: Center news & funding

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