Promise of Liquid Biopsy Enhanced by New Study Results

March 30, 2017
Promise of Liquid Biopsy Enhanced by New Study Results
Source: Penn Medicine

The results from three news studies, all led by investigators at the University of Pennsylvania Perelman School of Medicine, are set to be presented at the 2017 American Association for Cancer Research (AACR) Annual Meeting. The three studies focus on liquid biopsies, an innovation which uses blood tests instead of surgical procedures, with the hope of detecting cancer.

The first study is focused on biopsies and immunotherapy treatments for non-small cell lung cancer (NSCLC)—the most common form of the disease. One of the most promising immunotherapies for NSCLC targets the PD-1/PD-L1 pathway—which is known to suppress the immune system's ability to fight off cancer. These therapies inhibit this pathway, allowing the body to fight back. Currently, patients must undergo a biopsy to determine if they are candidates for this therapy.

Since obtaining biopsy tissue may cause patient discomfort and can sometimes be difficult or impossible to obtain due to the location of the tumor, the Penn researchers wanted to find a less invasive way to test these patients. They focused on malignant pleural effusions—fluid surrounding the lungs—which is a frequent complication in patients with advanced NSCLC.

"The common treatment for this is to drain the lungs; but as we do that, we can use that fluid to test the levels of PD-L1," explained lead study investigator Erica Carpenter, Ph.D., a research assistant professor of medicine in the division of hematology oncology at Penn. "The hope is that such a test, once clinically validated, may save the patient from undergoing a separate, invasive biopsy while still letting us find out if they are good candidates for checkpoint inhibitors."

For the study, the research team evaluated the pleural fluid from 66 patients. Researchers found circulating tumor cells (CTCs)—cancer cells that have moved into the blood stream—in 63 of the study subjects. Twenty-three percent of patients with a malignant pleural effusion were found to have detectable PD-L1 expression using this technique, similar to what has been previously observed. Dr. Carpenter said the results show this method may work on a larger scale, but that more research is needed. CTCs were also at the center of an additional study by Dr. Carpenter and her colleagues, which focused on clusters of those cells in the blood of prostate cancer patients.

"Scientists here at Penn Medicine and also at other institutions have shown that circulating tumor cell clusters, a phenomenon in which CTCs move through the blood in groups rather than alone as a single CTC, are particularly dangerous regarding metastatic spread, or cancer spreading throughout the body," Dr. Carpenter noted. "The ability to find and understand those clusters is crucial."

"Scientists here at Penn Medicine and also at other institutions have shown that circulating tumor cell clusters, a phenomenon in which CTCs move through the blood in groups rather than alone as a single CTC, are particularly dangerous in terms of metastatic spread, or cancer spreading throughout the body," Carpenter said. "The ability to find and understand those clusters is crucial."

In this second study, the investigators looked at 55 samples from 29 different patients. They found clusters of CTCs in 13 of the 29 patients (44.8%) and 19 out of the 55 samples (34.5%). The research team is focused on its next step, which is to compare these cluster counts with other blood-based measures like prostate-specific antigen (PSA) and Chromogranin A (CgA) to see if the number of clusters correlates with a more aggressive disease.

The third Penn study looked at CTC clusters in pancreatic cancer, with the aim of developing an approach to isolate those clusters out of the blood for analysis. "We have three goals here: find these cells, isolate them, then put them through RNA sequencing to discover unique aspects of their molecular makeup," Dr. Carpenter stated.

The team's approach includes the removal of red blood cells and other debris, leaving only the cells of interest as a sample. Researchers have already tested it in mice. The Penn researchers are optimistic that their work will lead to a noninvasive way to diagnose and monitor pancreatic cancer.