INNOVATION ARTICLES THE IDEA SUBMISSION PORTAL FROM MEDTRONIC

“Our lab is truly excited,” says Dr. David Wong. And they have good reasons to be. The UCLA scientist and his team believe that a new, non-invasive and highly accurate way of detecting cancer is just two years or less away.

The revolution in cancer diagnostics is all down to that most humble of bodily fluids, spit.

It sounds unbelievable to a layperson - something Dr. Wong is well aware of. Historically, he says, “saliva hasn’t received the attention of blood and other bodily fluids for clinical utilities, for a variety of reasons - social, cultural and behavioural. There’s been a notion that saliva is not as credible, for reasons that are not scientific.”

But Dr. Wong, Associate Dean for Research at UCLA and Director of the university’s Center for Oral/Head and Neck Oncology Research - and other researchers around the world - have found that saliva could be a key to early disease detection.

It’s been 12 years since full-blown research into saliva diagnostics began, Dr. Wong explains, and the research is now bearing fruit. Scientists around the world have found markers in saliva for certain cancers, including oral, pancreatic, gastric and lung cancer. In other words, research has shown that the saliva of people with cancer (and other conditions like diabetes and metabolic diseases) has a different make-up from the saliva of healthy people.

This finding, Dr. Wong predicts, will open up new technologies for disease diagnosis, change the way patients are treated, and, ultimately and most importantly, prolong and save lives.

In late 2014, Dr. Wong’s team published new findings after the most comprehensive analysis ever conducted of genetic RNA molecules in human saliva. They discovered RNA molecules in saliva which hadn’t been detected before, called extra-cellular non-coding RNA. And these genetic molecules are mutated in people with cancer.

Dr. Wong notes: “RNA has emerged in the last ten years as the central target in molecular biology. Watson and Crick found DNA, but 99 percent of the genome is non-coding sequences. For a long time scientists thought they were just junk DNA,” he says, but in the past 10 years we’ve learnt “that non-coding RNA are active and regulatory in nature”. And a new concept has been emerging in the last three years: that RNA can exist outside cells and serve like hormones - they are signalling molecules that send messages from a cell of origin to a target cell.

A saliva test for cancer would test for the presence or absence of mutated extra-cellular DNA and RNA.“Tumour cells shed tumour DNA and RNA into the circulation and they come into saliva,” Dr. Wong explains, “and mutations are detectable with unprecedented accuracy in saliva. Now we can look into the genome of someone with ovarian cancer or a brain tumour and look at every gene in their body, and find the genes that are mutated or altered. Those mutation profiles are reported and pharmaceutical companies are pouring their resources into finding drugs that can treat these mutations to prolong patients’ lives, amongst other benefits.”

Dr. Wong explains that all cancers have a genetic element. That doesn’t mean that they are hereditary - Dr. Wong clarifies that more than 90% of human cancers are “sporadic”, due to smoking or environmental carcinogens. But even sporadic cancers involve a genetic mutation, and it’s these mutations which saliva can reveal.

Companies are already offering saliva testing for women to find out if they have the BRCA genes associated with breast cancer. People have voiced concerns about the ethics of tests that reveal a risk of a disease, given that many identified as at risk will not develop the disease but could be caused significant worry. Dr. Wong emphasises that the testing he predicts for cancer is different. The DNA and RNA mutations his research shows up are “somatic” or acquired mutations and are actual markers of having cancer. He explains: “When that gene is mutated, you know this person has the cancer. It’s binary, black and white, there are no ifs and buts.”

He hopes we could see saliva testing of at-risk populations for certain diseases and stresses: “if you find the disease early, that’s the key to cure and to prolong life.”

Crucially, Dr. Wong says, saliva is more accurate and less invasive than other forms of testing. “The idea of liquid biopsy isn’t unique to saliva; it can be done in any body fluid,” he says. “But our current understanding is blood can detect about 80% of mutations in lung cancer at best, but saliva detects 100%. If you were a patient, what would you choose?”

Wong recently published a study which found that saliva can be used to detect with unprecedented accuracy in lung cancer patients whether they have lung cancer-associated mutations or not. He says: “To access this information ordinarily, a doctor would say to a patient: “I need to sedate you and do a bronchoscopy on your lung, get a biopsy of your tumour and look at whether this gene is mutated or not”.

“If we can obtain this info using a non-invasive means like saliva - liquid instead of tissue biopsy - it would be a fantastic outcome. Liquid biopsy is the hottest topic in cancer diagnostics right now, from scientific output to industry focusing on this area.”

For a blood test you need about 10ml of blood, but for a saliva test you only need about half of one drop. Also, a blood test result goes to a lab for testing, takes time to process, and costs money. “The scenario we are developing, Dr. Wong says, “is that the test can be done right now - in five minutes you will know the information. That could mean your tumour could be shrunk sooner - every second counts.”

What technology could this lead to? Anything from a testing unit for a doctor’s office to self-diagnostic devices for patients to monitor disease at home, Dr. Wong thinks. He himself works with outside industry partners to develop prototypes and on clinical trials, and says: “My hope and goal is that this technology could be in clinical practice and truly benefit patients.”

The fact that only certain cancers have been researched so far doesn’t mean that all cancers and other diseases may not also benefit from research in this area, Dr. Wong stresses. “In the past decade we have selected which diseases to look at first. If the future horizon continues to validate what we have embarked on, many if not most of human diseases, cancer, infectious disease, congenital disorders’ could be eased, he says. “Every cancer has a mutation basis to it - isn’t the genetic profiling of every human cancer the horizon we look forward to, the hope needed? There lies the excitement.”