Lung cancer is a leading cause of cancer death among men and women. By the time lung cancer is first detected, however, it often has already spread widely and is in advanced stages.
In an effort to move the needle forward to improve cancer detection techniques, the National Cancer Institute awarded $2.5 million over a period of five years to the UCLA School of Dentistry and the Department of Pathology and Lab Medicine at the David Geffen School of Medicine. The grant allows UCLA to clinically validate their liquid biopsy test, a rapidly emerging technology, with the goal to have it become a certified service at UCLA and beyond.
Current clinical practice for diagnosing lung cancer involves an invasive bronchoscopy, followed by genotyping of the captured cells for key indicators and mutations of lung cancer. Genotyping is the process of determining the genetic make-up of an organism. However, this process comes with challenges. Tumor biopsies aren’t entirely accurate and could have sampling errors, or may not be feasible depending on the health and age of the patient.
Liquid biopsy testing is a more effective, minimally invasive way to detect for key indicators in lung cancer. Current clinical liquid biopsy testing of blood and urine include, utilizing digital droplet PCR or next generation sequencing, both of which provide roughly 80 percent concordance with tissue biopsy genotyping.
“To our knowledge, this is the first grant of its kind from the National Cancer Institute that funds a liquid biopsy study for the detection of cancer mutations,” said principal investigator, Dr. David Wong, a professor of oral biology and associate dean for research at the UCLA School of Dentistry. “If our trial is successful, UCLA will be the only location in the country to offer this type of certified diagnostic testing of a patient’s blood or saliva.”
The trial will utilize the novel technology that Dr. Wong and his team developed two years ago. The test, called the electric field-induced release and measurement (EFIRM) liquid biopsy, detects actionable mutations in 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. Up until now, this method of testing has remained in the research lab and hasn’t yet reached clinical availability in hospitals and diagnostics labs.
“With support from the National Cancer Institute and our collaborative partnership with the UCLA Department of Pathology, Dr. Wong’s liquid biopsy test is poised to usher in a pivotal turning point in the fields of medicine and dentistry,” said Dr. Paul Krebsbach, professor and dean of the UCLA School of Dentistry.
The grant supports a two-phased clinical trial. The first phase of the trial, which will run for two years, will adapt, test and optimize the liquid biopsy test at the UCLA Molecular Diagnostic Laboratories. The second phase of the trial will use the refined liquid biopsy test to monitor patients who are at risk for non-small-cell lung cancer being seen at the Ronald Reagan UCLA Medical Center and the Veterans Affairs West Los Angeles Medical Center pulmonary disease clinics. The goal is to test results from 500 patients and compare the results to other digital droplet technologies.
“The EFIRM liquid biopsy technology detects key cancer mutations with nearly 100 percent concordance to other biopsy-based genotyping techniques,” said Wong, who also holds the Felix and Mildred Yip Endowed Chair in Dentistry. “However, the difference with our testing is that it is more accurate, non-invasive, real time, point-of-care, cheaper, and doesn’t require specialized access, equipment and trained personnel.”
Researchers hope that this trial will lead to more efficient and reliable test results, so that oncologists and cancer specialists can make more informed decisions about a treatment plan.
“This grant allows UCLA Health to partner with the UCLA School of Dentistry to introduce an exciting new technology into the clinical setting,” said Dr. Scott Binder, senior vice chair of pathology and laboratory medicine and director of pathology clinical services at UCLA Health. “Liquid biopsy testing will not only save lives, but also make it much more convenient for patients to get very accurate monitoring of their cancer disease state.”
By the end of the trial, the goal is to have the EFIRM-liquid biopsy test advance to a Clinical Laboratory Improvement Amendment-certified laboratory developed test and eventually become one of the diagnostic services offered at UCLA Health locations and UCLA Dental Clinics.
Other key investigators on this project include Fang Wei, PhD from the UCLA School of Dentistry; Dr. Guy Soo-Hoo from the Greater Los Angeles VA Medical Center; and Dr. Edward Garon, Dr. David Chia, Dr. Dean Wallace, David Elashoff, PhD, Dr. Wayne Grody and Dr. Rena Xian, all from the David Geffen School of Medicine at UCLA.
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, Wrigley and Colgate-Palmolive.