Accurately diagnosing the spread of cancer often involves painful and invasive biopsy procedures. The use of a “liquid biopsy,” which involves a simple blood draw, has been shown in a 5-year clinical trial to accurately detect and monitor certain kinds of breast cancer. The study involves circulating tumor DNA (ctDNA) and circulating tumor cells (CTC), genetic and cellular material from tumors that find their way into the patient’s bloodstream. A paper on the clinical trial’s results is published in JAMA Oncology.1 “These CTC cells are extremely rare,” says Cagri Savran, a professor of mechanical engineering at Purdue University. “In a blood sample of eight milliliters, there are billions of cells, but the cells we’re looking for, there may only be three or four.” Savran and his team at the Birck Nanotechnology Center in Purdue’s Discovery Park developed a liquid biopsy device to isolate these cells. They mix blood samples with magnetic particles, functionalized with antibodies to recognize the cells they are targeting. Then they run the samples through a microfluidic device, which has a magnetic field that attracts and captures only the magnetized CTC cells. “Once we’ve got them, we can do a number of things,” Savran says. “We can culture them, we can run tests on them, and, most importantly for this trial, we can count them. The number of cells in a sample has a significant meaning.” The device drew the attention of Milan Radovich, an associate professor at the IU Simon Comprehensive Cancer Center in Indianapolis and a 2004 Purdue graduate in biochemistry. “I focus primarily on the use of genomics for precision medicine in oncology,” Radovich says. “We really focus on figuring out what makes cancers tick, by looking at their DNA blueprint.” Radovich wanted to test the effectiveness of CTC detection as part of a larger clinical trial of 196 patients with triple-negative breast cancer. “This is a particularly aggressive form of breast cancer,” he said, “and recurrence of the disease tends to be high. So after their chemotherapy, we took blood samples from the patients to see if presence of the cells was an accurate marker of disease relapse.” Because IU Simon Comprehensive Cancer Center doesn’t have CTC technology, Radovich reached out to Purdue to test the samples. “Our novel microfluidic platform makes CTC detection simple, rapid, and scalable,” Savran says. “It takes longer to ship the samples than to complete the tests.” From 2014 to 2018, Radovich sent hundreds of blood samples to Savran, who isolated the CTC cells and reported their numbers back to Radovich. “Because this was a blinded study, neither of us could know the results until the trial was completed,” Radovich says. “It was a long 5 years to wait.” In the final analysis, their theory was proven right. “These circulating markers were more predictive of relapse than any other commonly used clinical marker on the planet,” Radovich says. “It’s more predictive than tumor size, grade, stage, or lymph node status.” “This is the largest clinical study ever published on the use of circulating markers and minimal residual disease,” Radovich says. “This really puts it on the map.” Both Radovich and Savran are now pursuing the future of non-invasive liquid biopsies. Savran patented the idea for his device through the Purdue Research Foundation Office of Technology Commercialization and created a company, Savran Technologies Inc., to make it commercially available. “It’s very important to me and my team of engineers that the things we build are really useful,” Savran said. “This technology is being used on real patients and now has the power to make a real difference.” Radovich plans to continue to use the technology in future clinical trials. “Imagine you’re a patient with this triple-negative breast cancer,” Radovich said. “Even if chemotherapy and surgery were successful, life can be a nightmare. They’ve told us that every headache or back pain incites fear that their cancer is coming back. With this technology, we can offer a more definitive answer for both physicians and patients.” Financial support for this study was provided by the Vera Bradley Foundation for Breast Cancer Research, Walther Cancer Foundation, Indiana University Grand Challenge Precision Health Initiative and Thomas Hurvis and McKinley Educational Foundation. Reference
- Radovich M, Jiang G, Hancock BA, et al. Association of circulating tumor DNA and circulating tumor cells after neoadjuvant chemotherapy with disease recurrence in patients with triple-negative breast cancer: preplanned secondary analysis of the BRE12-158 randomized clinical trial. JAMA Oncol. Epub. July 9, 2020. doi:1001/jamaoncol.2020.2295.
A “liquid biopsy” device developed by Purdue University engineers can accurately detect and monitor certain kinds of breast cancer. (Credit: Bin-Da Chan)