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Using blood, saliva, urine to detect cancer: Scientists’ ‘holy grail’

Testing for cancer in blood, urine or even saliva: That approach has been called the "holy grail" for diagnosing the second leading cause of death in the world, and it has been fueling an area of research that continues to raise eyebrows and questions

Testing for cancer in blood, urine or even saliva: That approach has been called the “holy grail” for diagnosing the second leading cause of death in the world, and it has been fueling an area of research that continues to raise eyebrows and questions.

Doctors can diagnosis cancers in a number of ways, including taking biopsies of tissue where a suspected tumor might be; imaging tests such as X-rays, ultrasounds or MRIs; and screening tests such as endoscopies or colonoscopies.

Yet some of those approaches can be uncomfortable for patients or may come with hefty medical bills, among other potential downsides.

For the future, many cancer researchers are exploring whether a cancer test could involve only collecting and analyzing a sample of your blood, saliva or urine so that it’s noninvasive, cheaper and more appealing to patients — especially when trying to diagnose cancer early.

These bodily fluids or liquid biopsies “have the potential to help clinicians screen for disease, stratify patients to the best treatment, and monitor treatment response and development of resistance,” the American Association for Cancer Research says.

The science behind detecting signs of cancer in liquid biopsies — and how that could change the patient experience and public health as a whole — remains in the early, experimental stages but has spurred some excitement.

Audience members whispered amongst themselves in a crowded conference room at the Georgia World Congress Center in Atlanta on Tuesday during the American Association for Cancer Research annual meeting, where cancer researchers and other medical professionals gathered to watch a panel of scientists present the latest data on using liquid biopsies to detect cancer.

Some attendees held their phones in the air to take photos of the presentation.

If liquid biopsies help detect cancer early, that would be beneficial — as the earlier cancer is detected, the better chances of survival — but much more research is needed, said Nickolas Papadopoulos, a professor of oncology and pathology at the Johns Hopkins Kimmel Cancer Center in Baltimore, who presented as part of that panel.

With detection, “it’s a difference of thinking proactively rather than reactively to this disease,” he said.

What the ‘holy grail’ of cancer tests could look like

Within the current body of liquid biopsy research, most studies seem to have focused on blood testing. There have been developments in creating blood tests to detect early stages of colorectal cancer and breast cancer, among others.

Still, this evolving research has some limitations. In general, cancer-screening tests can come with the risks of providing false positive or false negative results, overdiagnosis or even unnecessary treatments, all limitations to which blood tests could fall victim.

Overtreatment also can be a risk if a test detects a cancer that turns out to be slow-growing and therefore possibly harmless.

For instance, 1 in 3 women with breast cancer detected by a mammogram may be treated unnecessarily, because their screening tests found tumors that are slow-growing, according to a study published in the Annals of Internal Medicine in 2017.

On the other hand, finding cancer in an easy-to-collect blood test could improve survival rates when cancer is detected early and could be favorable among patients.

Being able to detect cancer from a simple blood draw compared with more invasive biopsies has been called the “holy grail,” not only for physicians but also for patients, said Medha Deoras-Sutliff, a two-time breast cancer survivor and executive director of The EHE Foundation, a nonprofit that focuses on a rare type of vascular tumor called epithelioid hemangioendothelioma.

Sutliff was first diagnosed with breast cancer 26 years ago, at the age of 27, after she told her primary care physician about a lump in her breast. She underwent a needle biopsy, during which a needle was forced into her breast at the site of the lump in order to pull out samples of it.

“Within a few minutes, they were able to look at it, and I got an answer it was benign,” said Sutliff, a graduate of the AACR Scientist-Survivor program.

“I thought that was OK, but we talked to a few other medical providers, and they thought, ‘Well, you can also get it removed, and you don’t have to think about it again,’ ” she said.

“I did remove it, and on examination after my surgery, they found, in another area of that lump, some suspicious cells. So that to me is how with biopsies, traditional biopsies, they pull sections from a certain area, and that’s it. But does that mean that the whole area of suspicion is uniform? Well, we know that’s not true,” she said. “Cancer is not the same in each patient and even within each tumor. A biopsy only looks at one specific area of a suspected tumor.”

Sutliff continued to monitor her breasts, and when she was 36, physicians noticed something suspicious on her mammogram.

This time, “I had to do a core needle biopsy,” she said. “You lay flat on a table, and you’re on your stomach, and your breast is placed in a hole, and your table is raised. The radiologist is under you, and you’re given a local anesthetic, and a hollow needle is guided into the breast.”

Her biopsy showed that she had breast cancer again, but it was in its early stages, and after treatment, Sutliff quickly recovered. However, the biopsies for both of her cancer diagnoses were “difficult,” she said.

If the future holds a simple blood test that could take the place of more invasive biopsies for some patients, that would be beneficial, Sutliff said.

“That holy grail is that blood draw will detect cancer in your blood, be able to determine where exactly that cancer may be in the body and hopefully tell us whether that cancer requires treatment,” she said.

A bloody evolution of cancer testing

Just last year, research on a newly developed blood test to detect multiple cancers was presented at the annual conference of the American Society of Clinical Oncology in Chicago.

The test screened for DNA from cancer cells and was able to detect 10 different cancers with good accuracy, according to the research.

The research involved 1,627 blood samples from 749 people with no cancer diagnosis and 878 people with newly diagnosed cancer that had not been treated.

It involved three tests on the participants’ blood samples and showed sensitivity in detecting 10 types of cancer: colorectal, esophageal, head and neck, hepatobiliary, lung, lymphoma, multiple myeloma, ovarian, pancreatic and breast.

The test most accurately diagnosed ovarian cancer, with 90% accuracy, followed by hepatobiliary — a highly lethal cancer that attacks the liver and gallbladder — and pancreatic cancer, with 80% accuracy.

However, it’s important to note that the number of people in which these cancers were detected was small. For both ovarian and pancreatic cancer, only 10 cases were detected, while only five people with hepatobiliary cancer were identified. Head and neck cancer as well as lung cancer were detected with the least accuracy: 56% and 59%, respectively.

The idea to use blood to screen for cancer, however, is nothing new.

“Blood tests have been traditionally involved in the initial assessment for the presence of various cancers. One ubiquitous example is the PSA test for the detection of prostate cancer,” said Liviu Movileanu, a professor of physics at Syracuse University in Syracuse, New York.

The prostate-specific antigen test measures the level of the PSA protein in a man’s blood to determine whether he has prostate cancer. The level of this protein produced by the prostate gland is increased above a critical value under the conditions of prostate cancer.

“Yet this and other protein biomarkers might undergo significantly amplified levels in the bloodstream even in noncancerous conditions,” Movileanu said.

“Therefore, our existing blood tests for cancer diagnosis are normally coupled with other procedures, such as imaging and biopsy tests,” he said, adding that more research is needed before blood tests for cancer diagnostics will no longer need those additional procedures to confirm results.

Movileanu and his colleagues have been conducting some of that research. Last year, they created a tiny sensor, called a nanopore, that can detect proteins in real time in samples of blood serum. This sensor was described in a recent paper in the journal Nature Biotechnology.

“The architecture of this sensor is quite generic, so that it can be applied to numerous serum proteins,” Movileanu said.

If this research and other studies on blood-testing approaches prove to be successful, cancer-screening tests could be “accomplished in a matter of minutes,” he said. “In this way, we will be able to screen an enormous amount of protein and DNA biomarkers.”

There also has been development in identifying which proteins and biomarkers researchers want to detect.

‘A universal blood test … is the ultimate goal’

Scientists at Mayo Clinic and a cancer diagnostics company called Exact Sciences have been collaborating on research to identify specific proteins or biomarkers tied to various tumor types. The idea is that if those biomarkers can be found in blood, they could be used to diagnose tumors in various areas of the body.

“We have identified biomarkers for 13 of the top 15 cancers,” including breast, colorectal and liver cancers, said Dr. Paul Limburg, a gastroenterologist at Mayo Clinic in Rochester, Minnesota, and co-chief medical officer of Exact Sciences.

Yet more work is needed before those biomarkers could be used to detect and diagnose cancers in patients at early stages.

“While more of the puzzle is being pieced together from a scientific perspective, it will still take years to conduct and complete the rigorous clinical research necessary to put these tests into everyday practice,” Limburg said.

“One of the challenges to developing a blood test to detect early-stage cancers is that the bloodstream only has minute levels of tumor DNA,” he said. “A blood test that can identify late-stage cancer may be closer, but the primary goal should be to detect cancer earlier, ideally even at a precancerous stage, when there is the best opportunity for curable treatment or even prevention.”

If early-stage cancers go undetected in a blood test or other type of liquid biopsy, that could put patients at risk of false negative results, said Dr. Ravi Salgia, professor and chairman of the City of Hope Department of Medical Oncology and Therapeutics Research in California.

Salgia and his colleagues have been studying ways to use blood tests to determine the best course of treatment for lung cancer patients who have been diagnosed, but to use blood testing to make that diagnosis remains to be seen.

“I do think we are optimistic about having that but are we close? In my mind, I don’t think so yet,” Salgia said.

Overall, “the future of cancer testing is compelling. If the promise of liquid biopsy holds true, patients and health care providers would have access to accurate and convenient tests that can detect cancer earlier,” Limburg said.

“A universal blood test — where one blood draw could tell you if and what type of cancer you have — is the ultimate goal and would be a major scientific and clinical breakthrough,” he said. “While challenges remain, both scientifically and from a regulatory perspective, it seems plausible that this type of breakthrough will be achievable within our lifetime.”

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