Research to Help Unlock the Mystery of How Cancer Spreads
Bioengineering Professor Mark Niedre and Assistant Professor Chiara Bellini received a 5-year, $2.7M grant titled “Continuous, Non-Invasive Optical Monitoring of Circulating Tumor Cell-Mediated Metastasis in Awake Mice” from the National Cancer Institute and National Institutes of Health.
Will the work of these Northeastern engineers help unlock the mystery of how cancer spreads?
One of the things that make cancer so sinister is that it’s rarely the first tumor that gets you. In fact, 90 percent of all cancer deaths are from tumors that have metastasized and taken root in other parts of the body.
Niedre is the principal investigator on a five-year, $2.7 million grant from the National Cancer Institute to develop a wearable device that can detect tumor cells that enter the bloodstream and circulate through the body. These escaped cancer cells are known as Circulating Tumor Cells or CTCs for short. Some of them form metastases.
“The scientific world has been studying CTCs for years, yet we still know very little about their dynamics—when they start to circulate, how long they stay in circulation, or how they fluctuate over time,” says Niedre.
The ultimate goal of the March 2022 grant is threefold: use mice to determine when and how many CTCs dislodge in the first place, better understand how they behave once they enter the blood stream, and even devise ways to prevent them from metastasizing.
For example, radiation therapy sometimes causes the release of tumor cells. But little is known about how or why this happens. Understanding the mechanics of this phenomenon would be the first step in preventing it.
“Maybe there’s something about radiation that makes cancer cells more aggressive, or maybe it causes an inflammatory reaction that causes the cells to move off the tumor,” says Niedre. “So this is one of the things we want to learn during this study and ideally how to block it.”
A Multidisciplinary Team
Bellini, who is an expert in constructing biomedical devices, will be in charge of adapting Niedre’s prototype optical blood sensor into a wearable device for mice.
“I’ve built many of the devices we use in lab,” she says. “In other projects, I’m working on an orthosis to induce scoliosis in mice and a robotic hand to help deaf and blind people communicate with sign language.”
The radiation portion of the study will focus on childhood brain cancer, which is why Niedre teamed up with Dr. Michael Taylor, a neurosurgeon at the Hospital for Sick Children in Toronto, Canada, who is an expert in medulloblastoma, a deadly form of pediatric brain cancer.
The team also includes Dr. Ross Berbeco, a member of the radiation oncology team at the Dana-Farber Cancer Center, and Dr. Scott Davis, an associate professor at Dartmouth College who specializes in tissue imaging.
A Potential Breakthrough
The current method for tracking CTCs is by taking a blood sample and examining it under a microscope—a method that has serious limitations.
“First of all, the blood samples are only 7.5 milliliters—about a half a tablespoon—which is less than one percent of a person’s blood supply,” says Niedre. “So it doesn’t give an accurate reading of the number of cancer cells in circulation. Second, those samples only show one moment in time, and the number of CTCs in circulation can vary enormously over short periods. If we take a sample now, that doesn’t mean the reading will be accurate an hour from now.”
A year ago, Niedre received another grant from the National Cancer Institute, to build a prototype of a revolutionary device that uses optical sensing to identify CTC cells in the bloodstream. The beauty of his device—known as a Diffuse in vivo Flow Cytometer (DiFC) — is that it can monitor CTCs continuously. In fact, it can evaluate the body’s entire blood flow in a matter of minutes.
DiFC can also monitor blood flow deeper in the body, which makes it capable of assessing the activity of most cancers.
However, the mice must anesthetized to use this prototype, which means it can only monitor for hour-long periods. A more serious limitation is that cancer behaves differently in awake, freely-moving and mice.
That’s why this collaborative work is so critical. By converting the current prototype into a wearable device, it will make it possible to monitor CTC activity 24/7 in mice that are awake and active.
The Big Picture
The long-term goal is to translate everything they learn from mice to humans. If successful, this new technology could revolutionize the way clinicians track the movement of tumor cells through the bloodstream and alert clinicians when cancer is likely to metastasize. Since the key to treating cancer is early detection, this could have life-saving implications.
“By better understanding when and why cancer metastasizes, we hope to find a way to mitigate that process,” says Niedre. “This isn’t pie-in-the-sky. We believe that the unique technologies we develop will have broad application to a broad range of cancers and anti-cancer therapies.”
The project will develop a new instrument (“w-DiFC”) for optically detecting and counting rare circulating tumor cells continuously and non-invasively in awake, freely-moving mice. The instrument will be used to study CTCs during metastasis development and in response to radiation therapy in mouse models of cancer. It is expected that w-DiFC will provide unique insights into metastasis biology and response to anti-cancer therapies. The project is in collaboration with Prof. Ross Berbeco at Dana Farber Cancer Institute in Boston, MA, Prof. Scott Davis at Dartmouth College, Hanover, NH, and Dr. Michael Taylor at the Hospital for Sick Children in Toronto, Canada.