Current methods to screen for lung cancer mutations in plasma or blood are complicated, technique-dependent and not readily available. Electric field-induced release and measurement is a reliable method to detect tumor-causing, lung cancer mutations in saliva that would be non-invasive, cost-effective and rapid. Clinicians could also use this technology to adjust their therapeutic strategies in real-time, improving clinical outcomes.
Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for 27 percent of all cancer deaths among both men and women, with about 225,000 new cases diagnosed in 2014, according to the American Cancer Society. Lung cancer kills more people than colon, breast and prostate cancers combined.
Early detection improves survival rates for people diagnosed with cancer, especially people diagnosed with lung cancer. Researchers from the UCLA School of Dentistry and collaborators from several other leading research institutions have discovered that a liquid biopsy of saliva may be as successful in detecting lung cancer as testing tissue that has to be surgically removed from the lungs.
A research team, led by Dr. David Wong, the school’s associate dean for research, completed a study that utilized a novel technology called electric field-induced release and measurement (EFIRM) to test lung cancer patients’ saliva for epidermal growth factor receptor (EGFR) gene mutations, a sign of lung cancer, which can be treated by medication such as thymidine kinase inhibitors.
The invasive approaches traditionally used by clinicians to gather sample tissues to look for EGFR mutations have limitations, though, including difficulty obtaining a sufficient number of tumor cells, that the sample is taken from a single snapshot in time or is subject to selection bias resulting from tissue heterogeneity. These methods are also invasive, expensive and time-consuming.
In EFIRM a multiplexible electrochemical sensor uses electrode chips to enable vesicular entities in saliva called exosomes to rapidly release molecular constituents (DNA, RNA and proteins) while simultaneously detecting any mutations in tumor-causing DNA sequences. The total detection time is less than 10 minutes and required a small saliva sample.
The key finding came from a blind and randomized clinical study that used saliva samples procured from lung cancer patients. Using the EFIRM method to detect two key tumor-causing mutations in the EGFR gene (L858R and exon 19 deletion) in saliva the researchers achieved nearly identical results as with bronchoscopy-based detection of the same two mutations.
Their findings have significant implications in the quest to develop more effective, non-invasive, reliable early detection testing for lung cancer mutations. Furthermore, EFIRM testing has the potential to show how the body is reacting to cancer therapeutics and whether those therapeutics need to be adjusted to improve a patient’s response.
The team was able to demonstrate that detecting EGFR mutations in saliva through the EFIRM method was just as effective as testing with plasma. Furthermore, the EFIRM method could be combined with tissue DNA testing or complement the biopsy in cases where the size of the tumors is insufficient for DNA extraction.
Dr. Fang Wei from the UCLA School of Dentistry; Chien-Chung Lin, Wu-Chou Su and Chung-Liang Ho, all from the Department of Internal Medicine, National Cheng Kung University Hospital; Aron Joon and Dr. Ziding Feng from the University of Texas, MD Anderson Cancer Center; Gabriel Troche, Maruja E. Lira, and Mao Mao, all from Pfizer, Inc.; Dr. David Chia from the UCLA Department of Pathology; and David T. W. Wong, lead author of the study.
Dr. Wong is the Felix and Mildred Yip Endowed Chair in Dentistry, professor of oral biology and the director for UCLA Center for Oral/Head & Neck Oncology Research at the UCLA School of Dentistry. He is also a member of UCLA’s Jonsson Comprehensive Cancer Center.
This research was supported by Faculty Seed Grants from the UCLA School of Dentistry (441901-69749-fangwei, F.W.), the Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH102-TD-C-111-003, C.C.L. and W.C.S), and the Taiwan Department of Health Cancer Research Center of Excellence (MOHW103-TD-B-111-06, C.C.L. and W.C.S).
Wong’s new research is published in the American Journal of Respiratory and Critical Care Medicine (AJRCCM) and will be featured on the cover of the Nov. 15 issue. The American Journal of Respiratory and Critical Care Medicine is a leading journal that focuses on human biology and disease.
David Wong is co-founder of RNAmeTRIX Inc., a molecular diagnostic company. He holds equity in RNAmeTRIX, and serves as a company director and scientific advisor. The University of California also holds equity in RNAmeTRIX. Intellectual property that Wong invented and which was patented by the University of California has been licensed to RNAmeTRIX. Wong is consultant to GlaxoSmithKlein, PeriRx, Wrigley and Colgate-Palmolive.