The spitting image of non-invasive diagnostics
LOS ANGELES—The U.S. National Institutes of Health’s (NIH) Common Fund has bestowed a $5 million award to researchers at the UCLA School of Dentistry to further their discovery that a patient’s saliva may be used to detect systemic disease—in this case, pancreatic cancer, which is typically diagnosed through an invasive and complicated biopsy.
Publishing their findings in a recent edition of the Journal of Biological Chemistry, the researchers are chasing the creation of a non-invasive tool that would enable clinicians and oncologists to detect pancreatic cancer through a simple risk-assessment test using saliva.
“There has been a long-known association of the mouth as a function of the body. Dentists can see evidence of systemic disease like diabetes and HIV. However, very little work has gone through due diligence,” says Dr. David Wong, the dentistry school’s associate dean of research and the Felix and Mildred Yip Endowed Professor in Dentistry. “For the very first time, the NIH has recognized that saliva biomarkers may be used for non-oral disease detection.”
Although recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected when a patient develops a systemic disease such as cancer of the pancreas, breast, lung and ovaries, the utility of salivary biomarkers for this purpose has been undermined by the absence of a biological and mechanistic rationale as to why distal diseases from the oral cavity lead to the development of discriminatory biomarkers in saliva. But Wong and his team hypothesized that tumor-derived exosomes are mechanistically involved in the development of pancreatic cancer-discriminatory salivary transcriptomic biomarkers.
“If we don’t have a scientific rationale and explanation for this, no one will look at this with credibility,” Wong notes.
To achieve that credibility, Wong’s team first developed a pancreatic cancer mouse model that yielded discriminatory salivary biomarkers by implanting the mouse pancreatic cancer cell line Panc02 into the pancreas of the syngeneic host C57BL/6. The role of pancreatic cancer-derived exosomes in the development of discriminatory salivary biomarkers was then tested by engineering a Panc02 cell line that was suppressed for exosome biogenesis, implanting into the C56BL/6 mouse and examining whether the discriminatory salivary biomarker profile was ablated or disrupted. Suppression of exosome biogenesis resulted in the ablation of discriminatory salivary biomarker development.
“The findings of this in-vivo study illustrated that the inhibition of pancreatic cancer-derived exosomes in mice altered the disease-specific salivary transcriptomic biomarker profile, supporting that tumor-derived exosomes play a role in the development of disease-specific discriminatory biomarkers in saliva,” the researchers concluded.
According to Wong, because this study does not provide the complete mechanistic explanation as to why and how communication occurs between a tumor distal to the oral cavity, future studies must be conducted to discover the path of the tumor-derived exosomes as they are secreted. As Wong and his colleagues concluded in their study: “Whether the interplay between tumor-derived exosomes and the salivary glands triggers disease-specific biomarkers will be the next focus. We will aim to examine whether tumor-derived exosomes are the shuttles that travel through the body’s vasculature and into the saliva delivering disease-specific messages, or whether they are messengers that trigger the release of secondary messengers (i.e., cytokines and hormones) inducing transcriptional modification of the salivary glands releasing biomarkers into the saliva.”
“Our long-term goal is to evaluate saliva biomarkers to monitor the early detection of systemic diseases like cancer of the pancreas, liver and lung. Our focus will be to take these biomarkers to the doorstep of the FDA. Anything short of that would just be academic writing,” says Wong.
That goal could be ultimately be used to create a non-invasive tool to detect pancreatic cancer using a patient’s saliva, eliminating the need for a patient to endure an invasive and complicated biopsy, says Wong.
“The holy grail of diagnostics is non-invasiveness. This new, emerging landscape is being viewed as transformative for biological science and clinical treatment,” he concludes.
The study, “Role of Pancreatic Cancer-derived Exosomes in Salivary Biomarker Development,” was published Sept. 13 in the Journal of Biological Chemistry.