How Circulating Tumor Cells Are Helping Kidney Cancer Patients

Josh LangLike many types of cancer, survival rates of kidney cancer have been rising significantly recently due to improved treatment options. However, despite new anti-cancer therapies and clinical trials in development, treatment resistance is common for most kidney cancer patients.


This March, for Kidney Cancer Awareness Month, Joshua Lang, MD, a medical oncologist with the UW Carbone Cancer Center, talks about advances in “liquid biopsies” for kidney cancer patients, where a blood draw – and not an invasive surgical biopsy – provides access to tumor cells circulating in the blood to monitor patients’ disease.


 “The challenge is that circulating tumor cells are very rare, about one tumor cell per every billion blood cells, so it’s orders of magnitude beyond finding a needle in a haystack,” Lang said. “People have been doing this in different types of cancers for a number of years, but it hasn’t worked well in kidney cancer.”


Lang, with initial funding from the Wisconsin Partnership Program, started a collaboration with UW Carbone urologist Jason Abel, MD, and biomedical engineer David Beebe, PhD, to develop a microscale platform to capture circulating tumor cells from blood samples generously donated by UW Carbone kidney cancer patients.


The technology works by placing a patient’s white blood cell sample onto a microchip. The tumor cells are hiding with the population of white cells, so to isolate them, the researchers add antibodies that bind to the proteins on the surface of kidney cancer tumor cells followed by magnetic beads that bind those antibodies. Then, they move an external magnet below the microchip to pull the cells bound by the antibody-bead complex through the microchip. The researchers can then analyze the molecular profiles of the circulating tumor cells, looking for differences in at the level of the genes, gene products, and proteins present in the cells. 


“It’s because of these microscale technologies that we essentially eliminate loss, and that really gives us the sensitivity we need to find these rare cells,” Lang said. “It allows us to do multiple complex assays on our rare samples.”


Having tested thousands of samples, the researchers have found that circulating tumor cells in kidney cancers express different types of proteins than those found in other types of cancers and that some of the more commonly found proteins in other cancers are completely absent in kidney cancer. This finding helps explain why capturing these cells was such a difficult task at the outset: many of the antibodies the researchers initially tested did not work to identify the surface proteins. The researchers are also trying to find patterns in their data about the amount of each gene product present in circulating tumor cells from kidney cancer.


With this new assay capable of finding circulating tumor cells in 80 to 90 percent of kidney cancer patients, Lang and his colleagues are now looking to see if these cells can serve as a biomarker to track patient treatment outcomes. The sensitivity of their assay allows the researchers to pick up on the individual differences between patients’ cancers, and they are developing clinical trials in collaboration with the Dana-Farber Cancer Institute.


For example, one clinical trial involved two immune therapies that have been shown to help some kidney cancer patients live longer – however, the treatments come with severe side effects. Researchers were looking at circulating tumors before and after the first treatment to identify which patients respond to see if they can spare these patients unnecessary side effects of the second treatment. Additionally, they hope to be able to leverage the information they gather from the treatment-resistant patients to develop new strategies for targeting that resistance.


“The more we know about our patients’ disease, the better information we can give our patients,” Lang says. “That’s really what precision medicine is about—getting the right treatments for the right people.”



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Date Published: 03/11/2019

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