Novel blood test could be first step to early detection of pancreatic cancer
Key takeaways:
- A novel blood test evaluating protease activity identified 85% of early-stage pancreatic cancer samples.
- The test could be used for other cancer types, as well.
A novel, rapid blood test demonstrated potential for detecting early-stage pancreatic cancer, according to results of a retrospective study.
The assay, named PAC-MANN, identified 85% of stage I pancreatic ductal adenocarcinoma (PDAC) samples when combined with CA 19-9.
“That’s critical,” Jared Fischer, PhD, assistant professor of molecular and medical genetics at Oregon Health & Science University and scientist at Cancer Early Detection Advanced Research Center (CEDAR) at OHSU Knight Cancer Institute, told Healio. “You don’t want to just be picking out late-stage cancer because then we’re not going to help the survival rate. You want to pick out early-stage cancers, and you want to pick that out at a high rate.”
Background
Pancreatic ductal adenocarcinoma (PDAC) causes the third most cancer-related deaths in the U.S., according to study background.
Patients diagnosed with late-stage, metastatic PDAC have a 5-year survival rate of only 3%.
Survival increases to 44% if the cancer is caught when it’s still localized, but early detection usually occurs by “accident,” Jose L. Montoya Mira, PhD, research engineer at CEDAR, told Healio.
Most patients come in with nondescript symptoms such as abdominal pain, which could be attributed to any number of diseases.
“There is no real test that is directly pointing at pancreatic cancer,” Montoya Mira said. “Pancreatic cancer usually comes out as a problem that is found from many other symptoms.”
CA 19-9 is the only FDA-approved biomarker for PDAC. However, it is approved only for monitoring response to treatment, not detection.
Numerous researchers have investigated methods to detect pancreatic cancer earlier.
Last year, Healio reported on a phase 2 trial of a novel evaluation of biomarkers that had associations with PDAC.
Researchers in that trial found adding CA199.STRA to CA 19-9 yielded a specificity of 0.94 and a sensitivity of 0.71.
The combination of CA199.STRA, LRG1 and CA 19-9 yielded a specificity of 0.65 and a sensitivity of 0.89.
Those results led researchers to begin a phase 3 trial.
Montoya Mira, Fischer and colleagues discovered the diagnostic potential of proteases for PDAC in previous research, and evaluated a new assay to see if they could improve those results.
“When there is a cell that is malignant, it’s been transformed. It needs to break out,” Fischer said. “In order for cancer to break out of that area and spread to other areas, these [proteases], these proteins are used to chew up the neighboring environment. If you could harness [the ability to detect] those proteins, theoretically you could detect cancer.”
Methods and results
Researchers used 110 pretreatment PDAC samples (mean age, 65.6 years; standard deviation, 10.1 years; 57% men) and 246 noncancerous samples (mean age, 63.2 years; standard deviation, 9.3 years; 59% men) from breast and prostate cancer screenings for their study.
Of the noncancer samples, 22% had pancreatitis and 12% had pancreatic neoplasia samples.
Researchers used a single-peptide probe to distinguish PDAC from control samples.
“We use a nanoparticle, and attached to that we have a mimic of what the protease likes to attack,” Montoya Mira said. “On the other side we have a molecule that emits light. We take that construct [and] put it in blood. If the protease is present and it’s also active, it will cut that mimic, and it will release that molecule that emits light into the solution. Then we can remove all the [nanoparticles] and just look at how much light is coming from that tube, and we're able to give you a response.”
The PAC-MANN assay had a 98% specificity and a 73% sensitivity across all stages of PDAC. Additionally, it had 100% accuracy distinguishing patients who had PDAC from those who had other pancreatic diseases.
When researchers combined PAC-MANN with CA 19-9, they got a 96% specificity in addition to 85% sensitivity for stage I PDAC.
“By combining our assay with CA 19-9, we can pick out patients with pancreatic cancer at an early stage,” Fischer said.
‘One step in the process’
The results — along with the simplicity and low cost of the test — have pleased both Fischer and Montoya Mira.
Current tests under investigation require significant sequencing, which involve “large amounts of blood and venous blood draws,” and results may take a couple weeks, Fischer said.
PAC-MANN only needs 8 µL of blood.
“Right now, it takes us 45 minutes from the time that we get the blood to get an answer, which is pretty awesome, and the metric that we have as a result is quite easy to understand by clinicians,” Montoya Mira said. “The cost is a little less than one cent per test. That’s the material cost — no specialized equipment. Just the two of us can run maybe 300 to 500 different samples in a day.”
Both Montoya Mira and Fischer emphasized this is just the first step.
They are hoping to start a clinical trial with high-risk patients, Montoya Mira said. They also would like to evaluate a longitudinal cohort.
Additionally, they plan to look at samples from other hospitals around the globe and examine if they could improve the probe’s engineering.
“You can change the [nanoparticle] size, you can change the material, you can change the length from the [nanoparticle] to the mimic, you can change the molecules that are emitting light and what they look like, you can change from light to other concepts like sequencing or [polymerase chain reaction],” Montoya Mira said. “There are so many of these systematic changes that need to be evaluated in order to improve that technology further.”
Adding another probe could be beneficial, as well.
“We’ve already done some studies and, when we multiplex it, it gets a lot better,” Fischer said.
The assay also could be used as early screening for other cancer types.
Montoya Mira, Fischer and colleagues plan to focus future research on cancers in the gastrointestinal tract, due to availability of resources at their university.
“I think there is a lot more that these markers can give us, not just in pancreatic cancer, but in many others, as well,” Montoya Mira said. “It opens the gate for not just us to keep doing the work and looking, but other people around the world to more actively look at the activity of these proteases in other cancers.”
However, Fischer cautioned this test would only be part of the diagnostic process for PDAC and other cancers.
“If your blood test comes up positive, you still need to be able to image it to know exactly where it is,” Fischer said. “We’re going to need imaging technologies to get better so you can pick up these smaller lesions so that we can help to find them earlier. This is just one step in the process of detecting cancer early.
“If our test were to ever pick out one person who has cancer [that otherwise] wouldn’t have been detected, I would be elated,” he added. “Obviously, you want to pick out everybody, but even just one person I would be proud. Hopefully, we can get to that point.”
For more information:
Jared M. Fischer, PhD, can be reached at fischerj@ohsu.edu.
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