A new ovarian cancer detection technique that utilizes nanopore sensing could help improve early diagnosis, according to a press release issued by the Biophysical Society.

Rockett TW, Almahyawi M, Ghimire ML, et al. Cluster-enhanced nanopore sensing of ovarian cancer marker peptides in urine. ACS Sens

Ovarian cancer has a 35% survival rate. In patients whose cancer has spread beyond the pelvis, the long-term survival rate drops to 20% or less. Only 20% of ovarian cancers are caught during stages I or II, a critical window for successful treatment. Symptoms can be vague —including bloating, pelvic or abdominal pain, feeling full quickly, or urination urgency or frequency—and hard to catch early on. 

Rockett TW, Almahyawi M, Ghimire ML, et al. Cluster-enhanced nanopore sensing of ovarian cancer marker peptides in urine. ACS Sens

Signs and symptoms of ovarian cancer | early signs of ovarian cancer.

Joseph Reiner, PhD, and colleagues at Virginia Commonwealth University want to improve those early diagnosis and survival rates. They found that nanopore sensing technology—designed to detect peptides—could pave the way to a urine-based test for ovarian cancer. 

This is where nanopore sensing comes into play: “The basic idea of nanopore sensing involves passing molecules through a tiny pore, or nanopore, and measuring the changes in electrical current or other properties as the molecules move through,” the press release explains. Nanopore sensing may allow clinicians to detect cancer-indicating peptides. In this case, peptides attach to the gold particle, showing a unique current signature.

Rockett TW, Almahyawi M, Ghimire ML, et al. Cluster-enhanced nanopore sensing of ovarian cancer marker peptides in urine. ACS Sens

Reiner tells MDLinx that he and his team previously reported on the selective detection of cysteine-containing peptides with a gold-modified nanopore approach, published in ACS Nano. Cysteine is known as a key player in cancer.

Ghimire ML, Cox BD, Winn CA, et al. Selective detection and characterization of small cysteine-containing peptides with cluster-modified nanopore sensing. ACS Nano. 2022;16(10):17229-17241.

Bonifácio VDB, Pereira SA, Serpa J, Vicente JB. Cysteine metabolic circuitries: druggable targets in cancer. Br J Cancer. 2021;124(5):862-879.

“Cysteine is one of the lowest abundance residues in the peptidome, and so it could serve as an ideal target for analyzing clinical samples because our system would be ‘blind’ to many—but not all—of the peptides in a sample, which would simplify analysis,” Reiner explains.  

“Working from these results, we decided to demonstrate our approach with ovarian cancer marker peptides in urine. This was motivated by the fact that ovarian cancer is one of the deadliest female reproductive cancers, in part because of the difficulties associated with early detection—and urine is a relatively easy bodily fluid to obtain,” he adds. 

The research team’s work made it possible to detect a number of these cancer marker peptides through assessing whether they’ve spiked in urine at high concentrations. 

The new method “identified and analyzed 13 peptides, including those derived from LRG‐1, a biomarker found in the urine of ovarian cancer patients,” the press release states.

The end goal? Reiner’s team hopes to detect ovarian cancer earlier by developing a test that combines with CA‐125 blood tests, transvaginal ultrasound, and analysis of family history.

Rockett TW, Almahyawi M, Ghimire ML, et al. Cluster-enhanced nanopore sensing of ovarian cancer marker peptides in urine. ACS Sens

“Our research team is currently focusing on optimizing sample preparation methods. If this approach is going to have real-world applications, it will require the ability to prepare the gold nanoparticles with target peptides outside the nanopore environment, as opposed to delivering the peptides directly onto the nanopore, as was done in this study,” Reiner and research author Gregory Caputo, PhD, of the Department of Chemistry & Biochemistry at Rowan University in Glassboro, NJ, explains to MDLinx.

They plan to focus on refining the preparation as well as demonstrating detection at lower peptide levels. “Our current limit of detection is in the low micromolar range. We will need to get into the nanomolar range in order for this to be workable,” they say. “It's worth noting that our results were from a single nanopore, but we envision this approach scaling up to hundreds or thousands of pores, and we believe this could help reduce the limit of detection for the technique.”

Their hope is that this method will eventually enable clinicians to test for different kinds of cancers and diseases. “It may also be possible to go even further and explore the impact of our approach on the detection of other types of medical conditions (eg, cardiovascular diseases, metabolic conditions, and various infections),” they say.