Researchers at the University of Toronto have developed an innovative technology to identify which patients might not respond to standard therapy for prostate cancer before it is delivered from a “liquid biopsy”.
Prostate cancer is the most common cancer in men (excluding non-melanoma skin cancers) and third leading cause of death in Canada, according to the Canadian Cancer Society 2017 statistics. While several viable treatment options for prostate cancer exist, many men affected with prostate cancer will not respond to first-line treatments.
“Screening for drug resistance is key to improving treatment approaches for many cancers,” says Shana Kelley, a professor at U of T’s Leslie Dan Faculty of Pharmacy. “It’s important for patients not to be on a therapy that won’t help them and it’s also important for health-care systems to avoid, whenever possible, delivering ineffective treatments.”
Creating an option for a “liquid biopsy” via a blood test instead of more invasive alternatives is a step in the right direction and will save time, money, and recuperation time.
Kelley, lead investigator on the study published in Nature Chemistry, explains how her team has advanced a completely new approach using magnetic nanoparticles with DNA capture probes on their surface that can target circulating tumour cells (CTCs) in blood samples to see if the cells contain biomarkers associated with drug resistance.
“We can then trap the individual magnetized cells in a microfluidic device built in the lab, isolating them from all the other cells in the sample and allowing us to perform highly sensitive analysis,” Kelley says. The cells with the highest magnetic content will also have high mRNA expression for the biomarker associated with drug resistance. This means that patients with high mRNA expression should be considered for other therapies because they won’t respond to the first-line treatment.”
Being able to access the CTC cells is critical in the fight against cancer, as they carry information from the primary tumour that will divulge the best form of treatment for the patient. They are, however, outnumbered by a billion-to-one by normal cells in a patient’s blood making catching them a very daunting task.
“Liquid biopsy is one of the most promising tools emerging for the management of cancer,” says Kelley. “We are excited about the potential of our technology to streamline this type of testing.”
In 2016, Kelley and her team published a study in Nature Nanotechnology that first introduced the microfluidic device and how it could be used to trap and analyze CTCs. The current study builds on this work by further targeting a specific biomarker within the CTCs.
The blood samples analyzed were collected from a small cohort of patients undergoing treatment for metastatic prostate cancer. In 10 of the patients tested, CTCs were visualized but only four of the patients exhibited the biomarker associated with drug resistance. This finding demonstrates that the new method can provide both a CTC count and an analysis of the clinically relevant biomarker.
“We are very excited because this is like finding a needle in a haystack,” says Kelley. “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.”
Further studies need to be conducted to ensure consistent findings. Kelley and her team would also like to take this technology and expand it to other forms of cancer and disease.