Texas A&M engineers illuminate cancer’s deadly hideout

Colorectal liver metastases (CRLM), cancer that has spread from the colon or rectum to the liver, have a deadly reputation. Due to its pervasive spread, typical cancer treatments like chemotherapy and surgical resection often prove ineffective. For the few patients who benefit from treatment, 75% still experience recurrence within two years and have poor survival outcomes.

Using the liver’s labyrinth-like surface as a hiding spot, cancer cells can evade treatment and conventional imaging, providing a false sense of hope for patients in remission. Cells tuck away into intricate ridges and folds of the liver and lie dormant until, seemingly out of nowhere, a sudden and aggressive tumor emerges.

In response, researchers from the biomedical engineering department at Texas A&M University — Drs. Shreya Raghavan, Alex Walsh, Daniel Alge and their respective labs — have teamed up to create models and imaging techniques to better understand and treat CRLM. 

“The thing with dormant, hidden cancer is that it is really hard to detect,” Raghavan said. “Our collaborators at MD Anderson tell us that they can’t see the tumors with conventional radiographic CT methods and images. If you can’t see them, you don’t know what unique therapeutic vulnerabilities they have. This is what inspired us to use engineering.”

Their findings, published in Advanced HealthCare Materials and Biomaterial Sciences, shed new light on a previously undetectable problem. Dr. Sabrina VandenHeuvel, study co-author and former graduate researcher from Raghavan’s lab, discovered that by growing colon cancer cells on a liver scaffolding material, she could mimic the dormancy effect clinicians were seeing in patients.

“This is a pretty big deal. We can engineer a model of dormant colon cancer liver metastasis,” Raghavan said. “Now we can begin to understand unique aspects of this disease that we can barely even detect clinically.”

After their initial discovery, Raghavan’s researchers hit a familiar roadblock. Like clinicians, they struggled to image the metastases using their traditional microscopy methods. That’s when Dr. Oscar Benavides — study co-author, department instructional assistant professor and former postdoctoral fellow in Walsh’s lab — introduced a more effective imaging method.

“The microscope that I use illuminates only a very thin plane, like five micrometers thick, which gives us really high spatial resolution,” Benavides said. “We can do 3D reconstructions by moving the sample along this plane. That’s something the original microscope did not have. They could only go about 100 microns deep, whereas I could go over 2,000.”

The NIH R37 MERIT program funded these works from the National Cancer Institute. In addition to their publications, the researchers developed an open-source imaging and machine learning platform freely available to other researchers to adapt and use for their own imaging and tissue engineering needs.

“We see this as a proof of concept to show we can generate these metastatic cancer models, and then we can develop imaging and analytical tools to actually pull out valuable clinical information,” Benavides said. “We put it out there into the literature for other groups to collaborate, or whoever else wants to investigate similar things.”

For future research, Raghavan said her lab is leveraging the expertise from Alge’s lab to create improved liver scaffolding systems and learn more about aspects of the liver that cause dormancy. In parallel, Walsh’s lab is refining microscopy methods to quantify whether there’s a treatment the metastases will respond to.

“We all play distinct roles in this bigger interdisciplinary project. We all have complementary expertise that is needed to take this beyond the research setting to clinical impact,” Benavides said. “By understanding how cells evade detection and recurrence, doctors could one day match the right drug to the patient’s unique metastatic disease, improving outcomes for the thousands facing colorectal liver metastases each year.”