Researchers have developed a chip that can analyze cells shed by lung cancer tumors in a patient's blood, allowing treating doctors to determine whether lung cancer treatment is working as early as the fourth week. The information provided by the chip will allow treatments to be tailored to meet patient needs and improve outcomes.
Stage 3 non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of lung cancers, and the current treatment method is a combination of chemotherapy and radiation therapy, followed by a year of immunotherapy. Assessing how a person is responding to treatment, and importantly assessing whether the cancer is likely to spread, takes time, which not every patient has a lot of time.
Now, University of Michigan (U-M) researchers have developed a chip that can analyze circulating cancer cells in a patient's blood and tell treating doctors by the fourth week how well their lung cancer treatment is working.
"Currently, we often have to wait weeks to months to fully assess the effects of cancer treatments," said Shruti Jolly, co-corresponding author of the study. "However, with this chip, we may be able to avoid long-term ineffective treatments and quickly switch to alternative treatments, thus sparing patients from unnecessary side effects." This technology has the potential to transform cancer diagnosis from delayed single assessment to more continuous monitoring, facilitating the delivery of personalized cancer treatments. "
CT scans are often used to determine whether a tumor has grown or shrunk, but only large changes are easily seen. Needle biopsies can provide more precise information, but this method is invasive and cannot be performed frequently to provide up-to-date information on a regular basis.
So researchers looked into liquid biopsies, a test that looks for signs of cancer in a patient's blood, such as cancer cells shed by tumors. Unlike needle biopsies, blood samples can be taken more frequently, but are only useful when the cells being tested reach detectable levels. Lung cancer has presented special problems in developing ways to monitor treatment through blood tests, researchers say, possibly because previous tests targeted a protein on the surface of cells that is not common in this cancer.
"We are looking for more sensitive cancer markers that can be used to closely monitor treatment," said Sunith Nagrath, another corresponding author of the study.
Nagras's research team developed the "GO chip" in 2013, which only captures circulating tumor cells (CTCs), successfully solving the shortcomings of other detection methods. Antibodies mounted on the chip's graphene oxide (GO, hence the name) nanosheets can recognize multiple cancer-specific protein markers on the surface of cells. As blood passes through channels in the chip, antibodies accumulate these markers, eventually collecting enough of them. Once trapped in place, researchers can count the cells, confirm whether they are cancer cells, and determine how the cells' biochemical properties differ between patients and at different stages of treatment.
To test whether the GO chip could monitor the effects of lung cancer treatment, researchers in this study collected CTCs from 26 stage 3 NSCLC patients who received chemotherapy and immunotherapy. Samples were collected before the start of treatment and after the first, fourth, tenth, eighteenth and thirtieth weeks of the patient's treatment.
They observed that CTCs decreased during treatment, and the greater the reduction, predicted a significantly longer progression-free survival (PFS). If the number of CTCs is not reduced by at least 75% by the fourth week of treatment, the patient's cancer is more likely to persist after treatment. The progression-free survival of these patients was 7 months, while the average progression-free survival of patients with a large reduction in CTCs was 21 months.
They also found that CTCs in cancer patients that did not respond to treatment activated genes that may make the cancer more resistant to drugs. This information may help develop targeted treatments, but further research is needed.
The research was published in the journal Cell Reports.