Cell-to-cell variation in gene expression creates a need for techniques that can characterize expression at the level of individual cells.
Prostate cancer is the second most common cancer in men and the fifth leading cause of death from cancer in men worldwide, according to 2012 numbers. While several viable treatment options for prostate cancer exist, many men affected with prostate cancer will not respond to first-line treatments.
University of Toronto researchers developed a liquid biopsy technology to improve prostate cancer treatment.
Credit: University of Toronto
Researchers in the Department of Pharmaceutical Sciences at the Leslie Dan Faculty of Pharmacy, University of Toronto have developed a new technology for liquid biopsy to identify which patients may not respond to standard therapy before it is delivered.
"Screening for drug resistance is key to improving treatment approaches for many cancers," said Shana Kelley, scientist and professor at the Leslie Dan Faculty of Pharmacy, University of Toronto. "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."
The ability to screen patients using a blood sample as opposed to more invasive techniques required for conventional biopsies is also a step forward.
Kelley, lead investigator on the study published today in Nature Chemistry, explained 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 contains 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 said. 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."
Targeting CTCs, the cells responsible for spreading cancer, is important because they carry information from the primary tumour that can inform treatment; however, they are outnumbered by a billion-to-one by normal cells in a patient' blood and are therefore extremely challenging to capture. 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 previous 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. 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," said Kelley.
As for next steps, the finding must be replicated in a larger study, Kelley explained. Her team is also focused on "scaling up" and expanding the application of this technology to other forms of cancer and other diseases.
"Liquid biopsy is one of the most promising tools emerging for the management of cancer," said Kelley "and we are excited about the potential of our technology to streamline this type of testing."
Kate Richards | EurekAlert!
Research offers clues for improved influenza vaccine design
09.04.2018 | NIH/National Institute of Allergy and Infectious Diseases
Injecting gene cocktail into mouse pancreas leads to humanlike tumors
06.04.2018 | University of Texas Health Science Center at San Antonio
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.
Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...
The Atlantic overturning – one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards – is weaker today than any time before in more than 1000 years. Sea surface temperature data analysis provides new evidence that this major ocean circulation has slowed down by roughly 15 percent since the middle of the 20th century, according to a study published in the highly renowned journal Nature by an international team of scientists. Human-made climate change is a prime suspect for these worrying observations.
“We detected a specific pattern of ocean cooling south of Greenland and unusual warming off the US coast – which is highly characteristic for a slowdown of the...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
18.04.2018 | Materials Sciences
18.04.2018 | Materials Sciences
18.04.2018 | Materials Sciences