The National Cancer Institute has awarded UNC Lineberger’s Shelley Earp, MD, and Yuliya Pylayeva-Gupta, PhD, a five-year, $2.69 million R01 research project grant to investigate approaches to overcome barriers to pancreatic cancer immunotherapies. Their objective is to understand resistance to modern immunotherapy and to design more effective combination therapies.
“The dismal outcomes of pancreatic cancer are, in part, due to the normal cells that infiltrate tumors; this tumor microenvironment works to thwart the immune system which otherwise could help eliminate cancer,” said Earp, who is director of the cancer center, the Lineberger Professor of Cancer Research and a professor of medicine and pharmacology at the UNC School of Medicine. “Several enzymes – the MerTK, Tyro3 and Axl receptor tyrosine kinases normally help to calm inflammation and repair tissues but in the tumor their action is subverted, and they inhibit the immune response. Our research will focus on the mechanisms by which these kinases hinder the immune response, and we will evaluate new, clinically applicable therapeutic agents that could synergize with current immunotherapies.”
The MerTK and Axl receptor tyrosine kinases were previously discovered, respectively, by the Earp lab and Edison Liu lab at UNC Lineberger.
Although the rates of some cancers have declined in the United States during the past few decades, the number of pancreatic cancer cases and deaths have been increasing since the late 1990s.
The American Cancer Society estimates that more than 64,000 people in the U.S. will be diagnosed with pancreatic cancer this year, and more than 50,000 will die from the disease, making it the fourth leading cause of cancer deaths in the country. It is predicted that pancreatic cancer will become the second leading cause of cancer deaths in the coming decades.
“Current therapies are largely ineffective against pancreatic cancer, and major parts of the problem are suppressive innate immune cells and fibroblasts in the tumor microenvironment,” said Pylayeva-Gupta, UNC School of Medicine associate professor of genetics and co-leader of Lineberger’s Immunology Program. “Our research will focus on answering some challenging questions, including: How do MerTK and Tyro3 kinases function in the innate immune compartment to accelerate pancreatic cancer growth and metastasis? Why does Axl have the opposite effect, and what is the role of Tyro3 in cancer-associated fibroblasts?”
Earp and Pylayeva-Gupta said the insights they hope to gain through this research could help scientists boost the effectiveness of current immunotherapies and potentially identify new therapeutic approaches to battle pancreatic cancer.