Using blood tests to advance cancer treatments

“It’s complicated for a lot of different reasons,” said Dr. Joshua Lang, a physician-scientist with the University of Wisconsin Carbone Cancer Center. “It’s not safe to do them repeatedly, there are other comorbidities associated with that.”

Lang, a prostate cancer specialist who studies why cancer becomes resistant to treatment, focused his attention on collecting cancer cells from a patient’s bloodstream – a process known as a liquid biopsy.

His lab partnered with that of Dr. Dave Beebe, an expert in biomedical engineering who developed a highly-sensitive microfluidic screen that can selectively collect relevant cells for study. The collaboration was so successful, Lang thought more researchers should have access to this technology.

“My prostate cancer lab was focused on patients with prostate cancer, but this need extends for basically every solid tumor,” he said.

This led to the 2017 creation of UW Carbone’s Circulating Biomarker Core, a shared service that processes a range of liquid biopsies to develop assays of various circulating biomarkers on behalf of researchers at the bench and clinical trial level.

Dr. Jennifer Schehr, facility manager of the core, said the circulating biomarkers they can recover through screening include circulating tumor proteins, DNA, and messenger RNA. That information can then be used by researchers to evaluate drug effectiveness or resistance.

In addition to blood draws being less invasive, those circulating tumor cells can have distinct features from cells in a patient’s primary solid tumor site.

“It’s a more comprehensive view,” Schehr said.

Lang, who serves as director for the core, has been impressed by its rapid growth in use. Their services have been used to support the work of 14 clinical trials, and the staff have processed thousands of blood samples from patients. They also receive samples to process from 22 cancer centers nationwide.

“Now we have projects in nearly every solid tumor, compared to a few years ago when we were literally just thinking up the idea,” Lang said.

One ongoing growth effort is to make their circulating tumor testing accessible in a clinic setting, so that treating physicians can evaluate the biomarkers unique to a patient’s cancer to see which treatments can work, and which will offer no benefit. A clinic use test requires proof that the testing is safe, replicable and demonstrates a patient benefit in a strictly regulated environment. As part of that initiative, the core partners with the UW Cytology facility at the Wisconsin State Lab of Hygiene.

Dr. Kaitlin Sundling, a co-director for the Circulating Biomarker Core, serves as director of the cytology laboratory for the Wisconsin State Lab of Hygiene. The cytology section is a clinically accredited facility that specializes in testing in bodily fluids for minute amounts of cells to diagnose diseases.

“It’s very natural for us to work on the circulating tumor assay that’s in development,” she said.

“Really this minimally invasive aspect, and doing more with less, is what we’re used to in cytology, so it’s really expanding what we can do with rare tumor cells, parts of tumor cells and getting into the molecular changes you can see in those cells.”

Lang is hopeful that a clinic use test will be approved by the end of the year.

The core also is expanding its capabilities in bioinformatics and sequencing, which Lang says will enable more complex genetic analysis of samples. Dr. George Zhao, a radiation oncologist who also has expertise in biomarker research and computational science, serves as co-director and lead bioinformatician for the core.

“I am excited about incorporating next-generation sequencing modalities into the services offered by the CBC,” Zhao said. “This includes sequencing of cell-free DNA/circulating tumor DNA, as well as RNA-sequencing of circulating tumor cells. This will expand the cutting-edge assays we can offer at the CBC.”