August 20, 2014
- Federico Innocenti receives a $275,000 NCI grant to study the role a cancer patient’s genetic makeup plays in the effectiveness of angiogenesis inhibitors.
- Angiogenesis inhibitors stop or slow the spread of tumors by choking off the blood supply that feeds them.
Angiogenesis inhibitors are a class of drugs commonly used in cancer therapy. However, there isn’t a way to identify patients who will benefit the most from treatment with these drugs.
A new $275,000 grant could help Associate Professor Federico Innocenti, MD, PhD, and his team identify such patients based on their genetic profile. Angiogenesis is the formation of new blood vessels that promote tumor growth.
Innocenti was awarded a two-year R21 grant from the National Institutes of Health and National Cancer Institute. R21 awards are given to encourage early-stage, high risk-high reward research. Nancy DeMore, MD, a surgeon at the UNC School of Medicine will collaborate with Innocenti on this project.
The UNC professors will use the money to study how genetic makeup can affect cancer prognosis or patient response to angiogenesis inhibitors.
The team will research genetic determinants of angiogenesis. They will also investigate how genetic variations influence the effectiveness of angiogenesis inhibitors.
Innocenti, who specializes in pharmacogenomics and cancer, says the framework that his team is using is groundbreaking.
“This will provide for the first time an understanding of how genetic variation impacts response to angiogenesis inhibitors,” Innocenti says. “It’s an essential component of studying pharmacogenetics of cancer patients being treated with this important class of drugs.”
The Framework
Amy Etheridge, the manager of Innocenti’s laboratory and a research specialist at the School, says the grant will build on the lab’s research investigating how genes influence cancer prognosis and therapeutics. The lab began its work in 2012 and includes three graduate students and one postdoctoral student.
“We’ve gotten preliminary data that has allowed us to identify genetic variants that associate with cancer prognosis and treatment response,” she says.
In order to clarify the role of these genetic variants in patient response, Innocenti’s lab is using genome editing to generate cell lines that differ at only a single base pair. This is key to understanding how treatment response varies based on genetics, Etheridge says.
“Working with DeMore’s laboratory, we will apply their expertise in using in vitro and in vivo assays of angiogenesis to see how these genetic changes affect angiogenesis and response to drug treatment in our experimental model,” she says.
“This would give us an idea of how these variants might be functioning and how patients would respond to angiogenesis inhibitors based on their genetic profile.”
Improving Cancer Treatment
This is a time where there’s an explosion of work being done on cancer treatment personalization, Innocenti says, which is exactly what the grant will further.
“It’s a way of researching individualized medicine—giving the right drug at the right dose at the right time to the right patient,” he says. “We’ll apply this to cancer patients where the side effects of chemotherapy are intense and some drugs aren’t as efficacious as we would like them to be.”
Innocenti, the author of more than 110 scientific publications, has dedicated his career to improving the treatment of cancer patients. His previous research with collaborators at the University of Chicago led to the use of the UGT1A1 genetic test to prevent the toxic side effects of cancer treatment with irinotecan.
He is currently the associate director of the UNC Center for Pharmacogenomics and Individualized Therapy and a member of the UNC Lineberger Comprehensive Cancer Center.
A native of Pisa, Italy, Innocenti received his MD and PhD in pharmacology, toxicology, and chemotherapy at the University of Pisa. Before coming to Chapel Hill, he worked as an assistant professor at the University of Chicago where he directed the pharmacology course for the Pritzker School of Medicine.
By Amanda Albright
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