Chip checks blood to see if cancer treatment is working by fourth week
Researchers have developed a chip that analyzes a patient’s blood for cells shed by a lung cancer tumor, enabling treating physicians to determine whether lung cancer treatment is working by as early as the fourth week. The information provided by the chip would allow treatment to be adapted to meet patient’s needs and improve outcomes.
The current treatment for stage 3 non-small cell lung cancer (NSCLC), which accounts for about 80% to 85% of lung cancers, is a combination of chemo- and radiation therapy, followed by a year’s worth of immunotherapy. Assessing how a person is responding to treatment and, importantly, whether the cancer is likely to spread requires time, which is not something that every patient has a lot of.
Now, researchers at the University of Michigan (U-M) have developed a chip that analyzes a patient’s blood for circulating cancer cells, telling treating physicians how well their lung cancer treatment is working by the fourth week.
“Currently, there’s typically a wait of weeks to months before we can fully assess the effectiveness of cancer treatment,” said Shruti Jolly, co-corresponding author of the study. “However, with this chip, we may be able to sidestep prolonged, ineffective therapy and quickly pivot to alternatives, thus saving patients from needless side effects. This technique has the potential to shift cancer diagnostics, moving from a delayed single assessment to a more continuous surveillance and facilitating the delivery of personalized cancer treatment.”
CT scans are usually used to determine whether a tumor has grown or shrunk, but only large changes are easily picked up. Needle biopsies can give more precise information, but they’re invasive and can’t be done frequently enough to provide regular updates.
So, the researchers looked at liquid biopsies, tests that look for signs of cancer in the patient’s blood, like cancer cells shed by tumors. Unlike needle biopsies, blood samples can be taken more frequently, but they’re only helpful if the cells being tested for are present in detectable levels. Lung cancer has proved a particular problem in terms of developing a means of monitoring treatment via a blood test, likely, say the researchers, because previous tests have targeted a single protein on the cells’ surface that’s not as common in this kind of cancer.
“We were looking for more sensitive markers of cancer that we could use to closely monitor treatments,” said Sunith Nagrath, the other of the study’s corresponding authors.
Nagrath’s team of researchers developed the ‘GO chip’ in 2013, which succeeded where other tests fell short by trapping only circulating tumor cells (CTCs). Antibodies mounted on the chip’s graphene oxide (GO, hence the name) nanosheets recognize a wide range of cancer-specific protein markers on the cells’ surface. As blood is pushed through channels in the chip, the antibodies accumulate these markers, eventually collecting enough to work with. Trapped in place, researchers can count the cells and confirm whether they’re cancerous, and determine how the cells’ biochemistry differs between patients and treatment stages.
To test whether the GO chip could monitor the effectiveness of lung cancer treatment, the researchers in the current study collected CTCs from 26 patients receiving chemoradiation and immunotherapy for stage 3 NSCLC. Samples were taken before treatment started and after the patients’ first, fourth, tenth, eighteenth and thirtieth weeks of treatment.
They observed that CTCs decreased during treatment, with a larger decrease predicting a significantly longer progression-free survival time (PFS). When the number of CTCs didn’t decrease by at least 75% by the fourth week of treatment, the patient’s cancer was more likely to persist after treatment. The PFS was seven months for these patients compared to the 21-month average in patients with a large decrease in CTCs.
They also found that CTCs from patients whose cancer didn’t respond to treatment had activated genes that may have made the cancer more resistant. This information may be useful in developing targeted treatments, but further study is required first.
The study was published in the journal Cell Reports.