Canadians Find Better Way to Screen for Drug-resistant Prostate Cancer

Canadians Find Better Way to Screen for Drug-resistant Prostate Cancer

A new approach to detecting tumor cells in the blood offers a minimally invasive alternative to identifying prostate cancer patients who may not respond to first-line treatments, Canadian researchers report.

They said the technology could be used to screen for drug-resistant tumor cells.

The study describing their approach, “Single-cell mRNA cytometry via sequence-specific nanoparticle clustering and trapping,” appeared in the journal Nature Chemistry.

“Screening for drug resistance is key to improving treatment approaches for many cancers,” Shana Kelley, a University of Toronto professor who was senior author of the study, said in a press release.

“It’s important for patients not to be on a therapy that won’t help them, and it’s also important for healthcare systems to avoid, whenever possible, delivering ineffective treatments,” she added.

The technology focuses on circulating tumor cells, which leave a primary tumor for the blood and can spread the cancer to other parts of the body.

Analyzing the cells is important because they provide information that can be crucial to treatment decision-making.

In tumors that are drug-resistant, circulating tumor cells often have high levels of particular messenger RNAs (mRNAs), or molecules that help genes produce proteins. This means the mRNA can be used as biomarkers of tumor drug resistance.

But capturing circulating tumor cells is challenging because they are present in very low numbers in the blood. The Toronto team’s technology is a step toward overcoming this problem.

Using magnetic nanoparticles containing probes for the mRNAs associated with drug resistance, researchers can trap the tumor cells in a microfluid device built in a lab.

The technique can identify tumor cells that could be unresponsive to drugs and isolate them from other cells in the blood so scientists can perform a more sensitive analysis.

Since this method is able to distinguish between tumor cells with high and low levels of mRNA, it can be used to identify patients who are likely to fail first-line treatment.

“This means that patients with high mRNA expression should be considered for other therapies because they won’t respond to the first-line treatment,” Kelly said.

The team analyzed blood samples of 11 patients being treated for metastatic castration-resistant prostate cancer. Their goals were to find the number of circulating tumor cells and the number of mRNAs associated with the cancer.

Researchers were able to see the circulating tumor cells in 10 out of the 11 patients. In four of them, the technique detected mRNAs associated with prostate cancer aggressiveness and hormone therapy resistance.

The findings demonstrated that the new method can both count the number of circulating tumor cells and analyze the mRNA biomarker.

“We are very excited because this is like finding a needle in a haystack. It paves the way for a straightforward and personalized screening tool that allows clinicians to see if a patient will respond to therapy or not. Our method is also rapid, accurate and inexpensive, which gives it real potential for clinical uptake,” Kelley said.

Researchers said larger studies are needed to replicate the findings and identify ways to optimize the detection of other mRNAs associated with prostate cancer.

“The technique will also need to be tested on early-stage cancer patients — whose samples typically exhibit much lower levels of CTCs [circulating tumor cells] — to investigate its utility for non-metastatic patients,” the researchers wrote.

They said they also plan to apply the technology to other forms of cancer and other diseases.