Liz Meszaros, MDLinx | March 30, 2017
In hopes of foregoing more invasive surgical procedures to properly diagnose and monitor cancer patients, researchers from the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, have focused on developing newer, non-invasive methods, and will present their findings at the upcoming 2017 American Association for Cancer Research (AACR) Annual Meeting in Washington, DC.
Specifically, these researchers have concentrated their efforts on earlier detection—via blood—of non-small cell lung cancer (NSCLC), prostate cancer, pancreatic cancer, and Barrett’s esophagus.
In NSCLC, immunotherapies targeting and inhibiting the PD-1/PD-L1 pathway, which has been shown to suppress the immune system’s ability to battle cancer, are promising. But, patients must first undergo a biopsy to determine if they are candidates for treatment.
To find a less invasive method of testing, Penn researchers focused on using malignant pleural effusions—a frequent complication in NSCLC patients—to test for levels of PD-L1, and thus determine which patients are candidates for therapy.
“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,” said the study’s lead author Erica Carpenter, MBA, PhD, research assistant professor of medicine, division of hematology/oncology, Perelman School of Medicine, University of Pennsylvania. “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.”
Dr. Carpenter and colleagues assessed malignant pleural effusions from 66 patients, and found circulating tumor cells (CTCs) in 63 of them. Thus, 23% of patients with a malignant pleural effusion had detectable PD-L1 expression using this new less invasive technology.
“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,” Dr. Carpenter said. “The ability to find and understand those clusters is crucial.”
Dr. Carpenter also focused research efforts on CTCs in patients with prostate cancer. She and fellow researchers assessed CTCs in 55 samples from 29 patients with prostate cancer, and found CTC clusters in 44.8% of patient (34.5% of samples). They will also compare these CTC cluster counts to other blood-based detection measures, including prostate-specific antigen (PSA) and chromogranin A (CgA) to determine if there are any associations between the number of clusters and more aggressive disease.
In a third study, Dr. Carpenters and colleagues focused on performing RNA sequencing of CTC clusters in patients with pancreatic cancer, in an attempt to find a way to isolate these clusters from the blood via removal of red blood cells and other blood components to help facilitate the diagnosis and monitoring of pancreatic cancer.
“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 explained.
Finally, a fourth study was conducted in patients with Barrett’s esophagus, and Dr. Carpenter and colleagues tested tissue obtained through endoscopy to develop a blood-based diagnostic.
“Our hope is that conducting molecular analysis of diseased and adjacent healthy tissue at a single cell level will inform eventual development of non-invasive patient monitoring. The ultimate goal would be development of a blood-based diagnostic for Barrett’s esophagus,” Dr. Carpenter said. “Our work may also help us understand how and why the disease sometimes progresses to esophageal cancer.”
Other contributors to this study include Anil Rustgi, MD, chief of Gastroenterology and T. Grier Miller Professor of Medicine and Genetics; Gary Falk, MD, MS, a professor of Gastroenterology and co-director of Penn’s Esophagology and Swallowing Center; Gregory Ginsberg, MD, a professor of Gastroenterology and executive director of Endoscopic Services; and John Lynch, MD, PhD, an associate professor of Gastroenterology, as part of their NCI-U54 funded Barrett’s Esophagus Translational Research Network (BETRnet) (U54-CA163004).
The lung and prostate cancer studies were supported, in part, by Janssen Pharmaceuticals, a division of Johnson & Johnson. The pancreatic and esophageal studies were supported, in part, by BD Technologies. The pancreatic study was funded by a grant from the National Institutes of Health (RO1CA207642) and by the Abramson Cancer Center’s Translational Centers of Excellence. The lung study was also supported by the Abramson Cancer Center’s Translational Centers of Excellence.