Tiny Worms Sniff Out Early-Stage Pancreatic Cancer

Donavyn Coffey

October 22, 2021

A new study suggests that tiny, clear nematodes can sniff out early-stage pancreatic cancer.

Research shows Caenorhabditis elegans (C elegans) are attracted to the odor certain chemicals give off — a behavior known as attractive chemotaxis — and early evidence indicates these scents may include human cancer cell secretions, cancer tissues, and urine from patients with colorectal, gastric, and breast cancers.

According to the recent analysis, published in Oncotarget, these small worms may be hot on the trail of pancreatic cancer-related compounds too. The researchers found that C elegans were significantly more attracted to patients with early-stage pancreatic cancer vs healthy controls.

There is a huge need for research like this that explores strategies to detect pancreatic cancer early, but it's far too soon to tell how, or if, this particular approach will be clinically relevant, according to Neeha Zaidi, MD, assistant professor of oncology and a medical oncologist specializing in pancreatic cancer at John Hopkins Medicine, Baltimore, Maryland, who was not involved in the current analysis.

Right now, few diagnostic markers exist for identifying pancreatic ductal adenocarcinomas (PDACs), which account for 90% of pancreatic cancers. PDACs remain one of the deadliest cancers, with a 5-year survival rate of 9%.

A combination of surgical resection and chemotherapy is the only curative treatment, and just 20% of patients are eligible, Zaidi said. The majority are identified after the disease has metastasized.

However, patients' 5-year survival rate improves markedly — as high as 85% — if the condition is caught sooner.

In the current study, the researchers first exposed C elegans to the urine of 83 patients from cancer centers across Japan who had various stages of pancreatic cancer before and after undergoing surgical resection. Using an assay, which takes 30 minutes and 50 to 100 nematodes per test, C elegans showed significantly higher chemotaxis toward preoperative urine compared to postoperative urine.

In a second, closed labeled arm, the nematodes were exposed to the urine of 28 randomized participants — 11 of whom had early-stage pancreatic cancer (0 or IA), plus 17 healthy volunteers. In this instance as well, C elegans showed significantly higher chemotaxis in patients with early-stage pancreatic cancer compared with healthy volunteers (P = .034). 

According to the authors, C elegans "had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers." And while this strategy needs to be further validated, they believe early detection of pancreatic cancer using C elegans "can certainly be expected in the near future." 

The study aligns with previous research, showing that wild-type C elegans are sensitive to scent and that these critters can smell cancer. Other studies have also found that sniffer canines can detect volatile organic compounds — including biomarkers of certain cancers — in the urine and breath of cancer patients. But training an adequate number of these canines for the clinic isn't feasible, while C elegans are far more compact and affordable.

According to Zaidi, a scent test using C elegans "seems pretty feasible" and cost effective, but whether this approach will "change our care has yet to be determined."

The authors, for instance, don't specify how the scent test will be used, though Zaidi suspects it would be most relevant for following patients with a higher risk of pancreatic cancer. Alternatively, it could be used as a screening test, but that's a massive undertaking and "this is way too early to tell if it's going to be helpful to use this test on a broad scale," Zaidi said.

To validate the approach, researchers would also need to know what exactly the C elegans are smelling and to test it in a much larger number of patients, Zaidi said. The mere 11 patients with cancer in the blinded portion of the study are not sufficient to draw any major conclusions.

The study also claims a high sensitivity, but what about specificity, Zaidi said. In other words, are there a lot of false positives? 

In addition, a deeper look at the participants shows the two groups — early PDAC and healthy volunteers — were not adequately balanced. The median age of the diseased patients is 70, and the healthy volunteers 39.

"This is a big difference," Eithne Costello, PhD, professor of molecular oncology at Liverpool University, United Kingdom, told Medscape Medical News via email. "It [also] appears the controls are all of one sex (either all male or all female), while the cancer group is mixed."

The authors attributed these shortcomings to the small population they had to work with: There simply aren't many patients whose pancreatic cancer is detected early. Zaidi agreed that patients with pancreatic cancer stage 0 or IA are extremely difficult to come by.

Even still, researchers need to understand the mechanisms behind this approach and see it work in a much larger group of patients, Zaidi said.  

Oncotarget. Published online August 17, 2021. Full text

The study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology. The authors reported institutional endowments received from Hirotsu Bio Science, Inc., Kinshu-kai Medical Corporation, IDEA Consultants, Inc., Ono Pharmaceutical Co., and others. Authors Nobuaki Kondo and Takaaki Hirotsu are employees of Hirotsu Bio Science, Inc.

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