The National Cancer Institute has awarded Chad Pecot, MD, a five-year, $1.835 million grant to support his research investigating the roles circular RNA may have in regulating whether a form of lung cancer will spread, or metastasize, beyond the original cancer site.
Lung cancer is the leading cause of cancer-related deaths in the United States, accounting for an estimated 127,000 deaths – or 20% of all cancer deaths – annually. While targeted therapies of lung adenocarcinoma have improved overall survival, there have not been similar advances in lung squamous cell carcinoma.
Pecot, associate professor in the Division of Oncology and director of the UNC RNA Discovery Center, said this research builds on findings from The Cancer Genome Atlas profiling studies, which revealed that squamous cell lung tumors are highly irregular and rarely driven by solitary actionable pathways. However, his lab found that a unique circular RNA, CDR1as, is an unexpected vulnerability for this difficult to treat cancer. In collaboration with Sarah Cohen, PhD, Pecot’s lab also found CDR1as cooperates with CDR1 to alter Golgi trafficking and cancer cell movement.
“We have uncovered a previously unappreciated CDR1as/CDR1 pathway that regulates squamous cell lung cancer metastasis and is highly associated with patient survival. This proposal seeks to uncover the fundamental mechanisms responsible for how CDR1 regulates lung squamous cell carcinoma metastasis through Golgi function, vesicular trafficking, and metastasis. We will also evaluate the biologic and therapeutic implications of targeting the CDR1as structure, which we think may result in an exciting new type of cancer treatment.”
Pecot said this research demonstrates the value and importance of the UNC RNA Discovery Center, which was established last year using UNC Lineberger funds to investigate all aspects of RNA biology, with the goal to make key discoveries in the basic and translational sciences and to study the various roles of RNA in health and disease.
“This is a highly collaborative proposal with several co-investigators in the UNC RNA Discovery Center. Our work with Kevin Weeks, PhD, and Qi Zhang, PhD, will integrate a multi-disciplinary approach to study RNA chemistry, structure, biology as well as cutting edge RNA-based therapeutics. Our mission in this proposal is to identify innovative therapeutic options for lung squamous cell carcinoma, which usually responds poorly to current treatment options. Our goal going forward will be to build off this success as we broaden our reach and foster more collaborations in the center,” Pecot said.