The grant will fund the development of cutting-edge technology that could detect colorectal cancer through a simple breath test
Leslie Chan and Vishal Manickam, graduate student who works on the design and testing of the ingestible probes.
Colorectal cancer is the second-leading cause of cancer death in the U.S., killing about 53,000 people each year. Traditionally thought of as a disease affecting the middle-aged and elderly, clinicians are seeing a rising number of cases in younger adults.
Currently, colonoscopies are the most effective early-detection method, scanning for visible changes in the colon. But they are invasive, a fact that often deters patients from getting screened.
“We really need diagnostic tests that are less invasive so that more people will adhere to recommended screening guidelines. Tests also need to be sensitive so we can catch colorectal cancer in its early stages, when it is the most treatable,” said Leslie Chan, assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
Chan and her lab are trying to meet that need. And the National Cancer Institute (NCI) is backing her with a prestigious $2.9 million R37 grant to develop cutting-edge technology that could detect colorectal cancer (CRC) through a simple breath test.
Chan and her team are creating ingestible nanosensors that sense dysregulated enzyme activities in the gastrointestinal tract — molecular-scale changes that occur during early tumor development. When the sensors detect these changes, they release volatile compounds exhaled in breath, basically creating synthetic breath biomarkers for CRC detection.
“What’s great is, our nanosensors will be made from compounds that are safe to ingest and are already found in our diets,” Chan explained. “For the volatile reporters, we’re using natural compounds and commonly-used additives that provide food with scent and flavor. We’ve worked with fruity and floral scents, as well as less pleasant smells like burnt rubber. This part of nanosensor development adds a little whimsy to an otherwise serious mission.”
Leslie Chan and her two graduate students - Vishal Manickam and Khoi Le - both of whom have contributed to the design of probes for sensing aberrant enzyme activities in the body.
Chan’s research team includes experts from biomedical engineering, oncology, immunology, and microbiology. The project is a collaboration with gastrointestinal cancer specialist Olatunji Alese and cancer immunology researcher Gregory Lesinski, both at Emory, and Illana Brito, a microbiome systems biology expert at Cornell University.
The early work to show feasibility of their nanosensor approach was completed by Chan’s first graduate student, Vishal Manickam.
“He demonstrated in mouse models that we could induce the exhalation of volatile reporters after oral administration of our nanosensors,” said Chan. “What we’ve developed sets the stage for not only colorectal cancer detection but many other hard-to-detect gastrointestinal diseases as well.”
Fecal biomarker tests have good sensitivity for advanced-stage CRC but struggle to detect early-stage disease. As a result, nearly 25% of cases are diagnosed after the cancer has spread, reducing the five-year survival rate by more than 70%.
“If successful, our nanosensor technology could revolutionize CRC screening and pave the way for breath-based detection of a wide range of GI diseases. We’re grateful to the NCI for supporting this work.” Chan said.
An R37 grant, or MERIT (Method to Extend Research in Time) Award, is one of the more significant grants from the NCI, given to outstanding early-stage investigators. It provides an initial five-year award with the possibility of a two-year extension after expedited review of achievements in the initial funding period.
Chan’s project will move forward with testing in animal models, with hopes of progressing toward clinical trials in the coming years.
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