Use of such precision diagnostics offer ‘early detection, localization, and the opportunity to monitor response to therapy,’ say the MIT scientists
Oncologists and medical laboratory scientists know that most clinical laboratory tests currently used to diagnose cancer are either based on medical imaging technologies—such as CT scans and mammography—or on molecular diagnostics that detect cancer molecules in the body’s urine or blood.
Now, in a study being conducted at the Massachusetts Institute of Technology (MIT), researchers have developed diagnostic nanoparticles that can not only detect cancer cells in bodily fluids but also image the cancer’s location. This is the latest example of how scientists are combining technologies in new ways in their efforts to develop more sensitive diagnostic tests that clinical laboratories and other providers can use to detect cancer and other health conditions.
Precision diagnostics such as molecular, imaging, and analytics technologies are key tools in the pursuit of precision medicine.
“Therapeutic outcomes in oncology may be aided by precision diagnostics that offer early detection, localization, and the opportunity to monitor response to therapy,” the authors wrote, adding, “Through tailored target specificities, this modular platform has the capacity to be engineered as a pan-cancer test that may guide treatment decisions for numerous tumor type.”
Development of Multimodal Diagnostics
The MIT scientists are developing a “multimodal” diagnostic that uses molecular screening combined with imaging techniques to locate where a cancer began in the body and any metastases that are present.
“In principle, this diagnostic could be used to detect cancer anywhere in the body, including tumors that have metastasized from their original locations,” an MIT new release noted.
“This is a really broad sensor intended to respond to both primary tumors and their metastases,” said biological engineer Sangeeta Bhatia, MD, PhD (above), in the news release. Bhatia is the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT and senior author of the study.
“It can trigger a urinary signal and also allow us to visualize where the tumors are,” she added. Bhatia previously worked on the development of cancer diagnostics that can produce synthetic biomarkers which are detectable in urine samples.
“The vision is that you could use this in a screening paradigm—alone or in conjunction with other tests—and we could collectively reach patients that do not have access to costly screening infrastructure today,” said Sangeeta Bhatia, MD, PhD (above), in the MIT news release. “Every year you could get a urine test as part of a general check-up. You would do an imaging study only if the urine test turns positive to then find out where the signal is coming from. We have a lot more work to do on the science to get there, but that’s where we would like to go in the long run.” (Photo copyright: NBC News.)
Precision Diagnostic Assists Assessment of Response to Cancer Therapy
For their research, the scientists added a radioactive tracer known as copper-64 to the nanoparticles. This enabled the particles to be used for positron emission tomography (PET) imaging. The particles were coated with a peptide that induced them to accumulate at tumor sites and insert themselves into cell membranes, producing a strong imaging signal for tumor detection.
The researchers tested their diagnostic nanoparticles in mouse models of metastatic colon cancer where tumor cells had traversed to the liver or the lungs. After treating the cancer cells with a chemotherapy regimen, the team successfully used both urine and imaging to determine how the tumors were responding to the treatment.
Bhatia is hopeful that this type of diagnostic could be utilized in assessing how patients are responding to treatment therapies and the monitoring of tumor recurrence or metastasis, especially for colon cancer.
What is unique about the approach used by Bhatia’s team is that one application of the copper-64 tracer can be used in vivo, in combination with imaging technology. The other application of the copper-64 tracer is in vitro in a urine specimen that can be tested by clinical laboratories.
“Those patients could be monitored with the urinary version of the test every six months, for instance. If the urine test is positive, they could follow up with a radioactive version of the same agent for an imaging study that could indicate where the disease had spread,” Bhatia said in the news release. “We also believe the regulatory path may be accelerated with both modes of testing leveraging a single formulation.”
The graphic above, taken from the MIT news release, shows how “multimodal nanosensors (1) are engineered to target and respond to hallmarks in the tumor microenvironment. The nanosensors provide both a noninvasive urinary monitoring tool (2) and an on-demand medical imaging agent (3) to localize tumor metastasis and assess response to therapy,” the news release states. (Photo and caption copyright: Massachusetts Institute of Technology.)
Precision Medicine Cancer Screening Using Nano Technologies
Bhatia hopes that the nanoparticle technology may be used as a screening tool in the future to detect any type of cancer.
Her previous research with nanoparticle technology determined that a simple urine test could diagnose bacterial pneumonia and indicate if antibiotics could successfully treat that illness, the news release noted.
Nanoparticle-based technology might be adapted in the future to be part of a screening assay that determines if cancer cells are present in a patient. In such a scenario, clinical laboratories would be performing tests on urine samples while imaging techniques are simultaneously being used to diagnose and monitor cancers.
Surgical pathologists may also want to monitor the progress of this research, as it has the potential to be an effective tool for monitoring cancer patients following surgery, chemotherapy, or radiation therapy.
This research could lead to a useful liquid biopsy test that would be a powerful new tool for clinical laboratories and anatomic pathologists
Cancer researchers have long sought the Holy Grail of
diagnostics—a single biomarker that can quickly detect cancer from blood or
biopsied tissue. Now, researchers in Australia may have found that treasure. And
the preliminary diagnostic test they have developed reportedly can return
results in just 10 minutes with 90% accuracy.
In a news release, University of Queensland researchers discussed identifying a “simple signature” that was common to all forms of cancer, but which would stand out among healthy cells. This development will be of interest to both surgical pathologists and clinical laboratory managers. Many researchers looking for cancer markers in blood are using the term “liquid biopsies” to describe assays they hope to develop which would be less invasive than a tissue biopsy.
“This unique nano-scaled DNA signature appeared in every type of breast cancer we examined, and in other forms of cancer including prostate, colorectal, and lymphoma,” said Abu Sina, PhD, Postdoctoral Research Fellow at the Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), in the news release.
“We designed a simple test using gold nanoparticles that
instantly change color to determine if the three-dimensional nanostructures of cancer
DNA are present,’ said Matt
Trau, PhD, Professor of Chemistry at the University of Queensland, and
Deputy Director and Co-Founder of UQ’s AIBN, in the news release.
The team’s test is preliminary, and more research is needed before
it will be ready for Australia’s histopathology laboratories (anatomic
pathology labs in the US). Still, UQ’s research is the latest example of how
increased knowledge of DNA is making it possible for researchers to identify
new biomarkers for cancer and other diseases.
“We certainly don’t know yet whether it’s the holy grail for
all cancer diagnostics, but it looks really interesting as an incredibly simple
universal marker of cancer, and as an accessible and inexpensive technology
that doesn’t require complicated lab-based equipment like DNA sequencing,” Trau
added.
The UQ researchers published their study in the journal Nature Communications. In it, they noted that “Epigenetic reprogramming in cancer genomes creates a distinct methylation landscape encompassing clustered methylation at regulatory regions separated by large intergenic tracks of hypomethylated regions. This methylation landscape that we referred to as ‘Methylscape’ is displayed by most cancer types, thus may serve as a universal cancer biomarker.”
While methyl patterning is not new, the UQ researchers say they were the first to note the effects of methyl pattern in a particular solution—water. With the aid of transmission electron microscopy, the scientists saw DNA fragments in three-dimensional structures in the water. But they did not observe the signature in normal tissues in water.
“To date, most research has focused on the biological consequences of DNA Methylscape changes, whereas its impact on DNA physicochemical properties remains unexplored,” UQ scientists Matt Trau, PhD (left), Abu Sina, PhD (center), and Laura Carrascosa (right), wrote in their study. “We exploit these Methylscape differences to develop simple, highly sensitive, and selective electrochemical or colorimetric one-step assays for the detection of cancer.” (Photo copyright: University of Queensland.)
Their test averaged 90% accuracy during the testing of 200
human cancer samples. Furthermore, the researchers found the DNA structure to
be the same in breast, prostate, and bowel cancers, as well as lymphomas, noted
The Conversation.
“We find that DNA polymeric
behavior is strongly affected by differential patterning of methylcytosine
leading to fundamental differences in DNA solvation and DNA-gold affinity
between cancerous and normal genomes,” the researchers wrote in NatureCommunications.“We exploit
these methylscape differences to develop simple, highly sensitive, and
selective electrochemical or one-step assays for detection of cancer.”
Next Steps for the
“Gold Test”
“This approach represents an exciting step forward in
detecting tumor DNA in blood samples and opens up the possibility of a generalized
blood-based test to detect cancer, Ged Brady, PhD, Cancer Research UK
Manchester Institute, told The
Oxford Scientist. “Further clinical studies are required to evaluate
the full clinic potential of the method.”
Researchers said the next step is a larger clinical study to
explore just how fast cancer can be detected. They expressed interest in
finding different cancers in body fluids and at various stages. Another opportunity
they envision is to use the cancer assay with a mobile device.
DiCarlo told USA Today
that such a mobile test could be helpful to clinicians needing fast answers for
people in rural areas. However, he’s also concerned about false positives. “You
don’t expect all tumors to have the same methylation pattern because there’s so
many different ways that cancer can develop,” he told USA Today. “There
are some pieces that don’t exactly align logically.”
The UQ researchers have produced an intriguing study that differs
from other liquid biopsy papers covered by Dark Daily. While their test may need to be used in combination with other
diagnostic tests—MRI, mammography, etc.—it has the potential to one day be used
by clinical laboratories to quickly reveal diverse types of cancers.
Concept is for patients to take a pill containing nanoparticles programmed to detect cancers or other disease symptoms and a wearable gadget would report their findings
Google is using the same biomarker molecules as clinical laboratories in an attempt to enable in vitro monitoring of an individual’s health status. The device is under development and represents yet one more effort by Google (NASDAQ:GOOG) to penetrate the market for consumer health services.
This futuristic project is under development by the Google X Life Sciences team. The goal is create a device that would allow patients to noninvasively self-diagnose most diseases and health conditions.
The team is led by Andrew Conrad Ph.D.. The device under development is called the NanoParticle platform. It is a tool that continuously monitors an individual’s health status from the inside and reports what it finds through a wearable, watch-like device. (more…)
The ATC Chip identifies ovarian cancer cells floating in ascites and may be useful for diagnosing other types of malignancies that involve ascites, like pancreatic cancer
Pathologists will be interested to learn that researchers at Harvard Medical School and Massachusetts General Hospital are developing a “liquid biopsy” technology specifically to enable point-of-care monitoring of the progress of patients undergoing treatment for certain types of cancers.
The goal is to develop a method that community hospitals can use to monitor treatment of ovarian cancer patients without the need for expensive medical laboratory equipment, noted a report published by Biosciencetechnology.com. Researchers estimate that their ‘liquid biopsy’ technology could cost as little as $1 per test when eventually cleared for use in clinical settings. (more…)
Up to 400 times more sensitive than existing ELISA-based methods
Detecting any of seven cancers in their earliest stages may be feasible through the use of a new biomarker chip that was recently unveiled by scientists from Stanford University’s Center for Magnetic Nanotechnology. To give their biomarker chip increased sensitivity over fluorescent detection methods, the scientists use magnetic technologies to accomplish detection.
Reporting in Proceedings of the National Academy of Sciences (PNAS), lead scientist Shan X. Wang, Ph.D., director of the center and professor of materials science and electrical engineering, says the chip is able to detect very low levels of seven cancers. The biodetection chip is to be marketed by Silicon Valley startup MagArray Inc., of Sunnyvale, California. It detects multiple proteins in blood or DNA strands using magnetic technology similar to how a computer reads a hard drive. Developers say this chip could also be used to diagnose cardiovascular disease and monitor cancer therapy.
