According to the American Cancer Society, worldwide, lung cancer is the leading cause of cancer-related deaths, accounting for 27% of all cancer deaths among both men and women; in 2014, 225,000 new cases were diagnosed in the US. The malignancy kills more people than colon, breast, and prostate cancers combined. Current screening methods for lung cancer mutations in plasma or blood are complicated and not readily available. Researchers at the UCLA School of Dentistry, together with colleagues at other research facilities, have developed a new detection method that requires a saliva sample. They published their findings on November 15 in the American Journal of Respiratory and Critical Care Medicine (AJRCCM); the article is featured on the journal’s cover. The AJRCCM concentrates on human biology and disease.
The researchers developed a detection method known as electric field-induced release and measurement (EFIRM); they note that it is a reliable technique to detect tumor-causing, lung cancer mutations in saliva. The procedure is non-invasive, cost-effective, and rapid. Physicians and other healthcare professionals could use the technology to adjust their therapeutic strategies in real-time; thus, improving clinical outcomes.
The investigators stress that early detection improves survival rates for individuals diagnosed with cancer, particularly those diagnosed with lung cancer. They note that they have discovered that a liquid biopsy of saliva may be as accurate in detecting lung cancer as testing tissue that is surgically removed from the lungs. The research team, led by Dr. David Wong, the dental school’s associate dean for research, studied EFIRM to test lung cancer patients’ saliva for epidermal growth factor receptor (EGFR) gene mutations, which is a sign of lung cancer that can be treated by medication such as thymidine kinase inhibitors.
The study authors note that the invasive approaches traditionally used by clinicians to obtain sample tissues to detect EGFR mutations have limitations, including difficulty obtaining a sufficient number of tumor cells; it is a sample is taken from a single snapshot in time or is subject to selection bias resulting from tissue heterogeneity (variation in the type of cells present). The EFIRM procedure is an electrochemical sensor, which uses electrode chips to facilitate substances in saliva called exosomes to rapidly release molecular material (DNA, RNA, and proteins) while concurrently detecting any mutations in tumor-causing DNA sequences. The total detection time takes less than 10 minutes and requires only a small saliva sample.
The crucial finding came from a blinded and randomized clinical study that used saliva samples obtained from lung cancer patients. Using the EFIRM technique to detect two major tumor-causing mutations in the EGFR gene (L858R and exon 19 deletion) in saliva, the investigators attained nearly identical results as with bronchoscopy-based detection of the same two mutations. The researchers note that their findings have significant implications in the search to develop more effective, non-invasive, reliable early detection testing for lung cancer mutations. In addition, EFIRM testing has the potential to demonstrate how the body is reacting to cancer treatments and whether those treatments need to be modified to improve a patient’s response.
The researchers demonstrated that the detection of EGFR mutations in saliva via the EFIRM method was just as effective as testing with plasma. In addition, the EFIRM method could be combined with tissue DNA testing or supplement the biopsy sample in cases where the size of the tumors is inadequate for DNA extraction. In addition to UCLA, the researchers are affiliated with: the Department of Internal Medicine, National Cheng Kung University Hospital, Taiwan; the University of Texas, MD Anderson Cancer Center; Pfizer, Inc.; and UCLA Department of Pathology.