News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
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Harvard Researchers Create Chip-based, Liquid Biopsy Device That Offers a Novel Way to Monitor Treatment of Ovarian Cancer Patients and Only Costs $1

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.
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Using Extracellular Vesicles, Researchers Highlight Viability of Liquid Biopsies for Cancer Biomarker Detection in Clinical Laboratories

Identification of 144 elevated phosphoproteins indicative of cancer shows one possible path forward in the use of liquid biopsies for early detection of cancer and monitoring patients in remission

While precision medicine and a growing menu of medical laboratory assays and diagnostics are increasing the number of treatment methods available to cancer patients, early detection is still key to improving outcomes and increasing the odds of survival.

In February 2017, a Dark Daily ebriefing titled, “British Medical Laboratory Test for Early Screening of Lung Cancer Shows Promising Interim Results in Large Trial; Could Lead to Other Simple Blood Tests for Cancer Detection,” showcased the EarlyCDT-Lung test. In a University of Dundee press release, researchers noted the non-invasive test promised detection of lung cancer “potentially up to five years” earlier than traditional scans.

Now, researchers from Purdue University are testing a non-invasive blood test for detection of all types of cancer using phosphoproteins as biomarkers that could detect cancer even before the onset of any symptoms. This could lead to non-invasive therapies, and ways to monitor them, that could be applied while the patient’s body is still strong and able to respond well to treatment.

Speaking with New Atlas, researcher W. Andy Tao, PhD, Chief Scientific Officer of Tymora Analytical Operations, stated, “This is definitely a breakthrough, showing the feasibility of using phosphoproteins in blood for detecting and monitoring diseases.”

Extracellular Vesicles as the Key to Isolating Phosphoproteins

Protein phosphorylation—particularly mutations in phosphatases and kinases—are already known to play roles in cancer development as noted in the OncLive article “Phosphorylation: The Master Switch of the Cell.”

However, as the liver uses phosphatase to dephosphorylate proteins, identification of phosphoproteins in the blood has remained difficult for researchers.

Isolating phosphoproteins from tissue samples is equally difficult. “Assays of phosphoproteins from tissues face tremendous challenges because of the invasive nature of tissue biopsy and the highly dynamic nature of protein phosphorylation during the typically long and complex procedure of tissue biopsy,” noted I-Hsuan Chen, PhD Candidate, and W. Andy Tao, PhD, in their study published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

As shown in the illustration above, extracellular vesicles are basically blobs of cellular cytosol that contain microRNA (miRNA) Messenger RNA (mRNA) and proteins, which some researchers believe potentially could compete with stem cell-based therapeutics. (Image copyright: BioProcess Intl.)

In their attempts, researchers instead focused on the biomarker discovery potential of extracellular vesicles (EV)—in particular microvesicles and exosomes—citing strong evidence in the ability to use EV-based disease biomarkers well before symptoms appear.

“The ability to detect the genome output (active proteins, and in particular phosphoproteins) can provide more direct real-time information about the organism’s physiological function and disease progressions, particularly in cancers,” the PNAS study authors noted.

Researchers isolated nearly 2,400 phosphoproteins across 30 samples from breast cancer patients. They then compared these to six control samples and identified 144 specific proteins commonly elevated when cancer was present.

In a Purdue University press release, Timothy Ratliff, PhD, Director of Purdue University Center for Cancer Research expanded on the findings of the study, stating, “The vesicles and exosomes are present and released by all cancers, so it could be that there are general patterns for cancer tissues, but it’s more likely that [W. Andy Tao, PhD] will develop patterns associated with different cancers.”

Monitoring Cancer with a Blood-Based Cartridge Diagnostic

The Purdue University press release highlights the potential of the process, noting, “A simple blood test for cancer would be far less invasive than scopes or biopsies that remove tissue. A doctor could also regularly test a cancer patient’s blood to understand the effectiveness of treatment and monitor patients after treatment to see if the cancer is returning.”

The ability to capture EV phosphoproteins appears to be stable over time. The samples used in the Perdue University study were taken nearly five years ago by the Indiana Biobank.

While the stability of samples is a boon to researchers, they note that there are still many improvements to be made to the methods used before some medical laboratories could attempt to replicate their results.

Current methods require using differential high-speed and ultra-high-speed centrifugation. Study authors note this makes it less than ideal for clinical laboratory use due to lack of access and lower specificity.

However, the Purdue press release also notes plans for future improvements. Tymora Analytical Operations is developing technologies to use the biomarkers in a cartridge-based system. This could mean that pathology groups and medical laboratories might one day add an automated test to their menus for the second leading cause of death in the United States.

Until then, medical laboratories can help further efforts by collecting samples and working with biobanks, such as the one used in the Purdue study. Clinical laboratories already power much of the diagnostic tools driving innovation and discovery in oncological precision medicine. With the addition of a way to detect cancers, both while in remission or before symptoms appear, laboratories could further increase their role in fighting this worldwide killer.

—Jon Stone

Related Information:

Protein Discovery Points to Potential Blood Test for All Cancers

Phosphoproteins in Extracellular Vesicles as Candidate Markers for Breast Cancer

Breakthrough Discovery May Make Blood Test Feasible for Detecting Cancer

Phosphorylation: The Master Switch of the Cell

Overview of Protein Phosphorylation

Extracellular Vesicles Commercial Potential as Byproducts of Cell Manufacturing for Research and Therapeutic Use

Extracellular vesicles: An Introduction

British Medical Laboratory Test for Early Screening of Lung Cancer Shows Promising Interim Results in Large Trial; Could Lead to Other Simple Blood Tests for Cancer Detection

Sound Wave Acoustic Tweezers Locate and Isolate Circulating Tumor Cells in Liquid Biopsies; Could Lead to Less Invasive Cancer Diagnostics and Treatments

Pathologists will be interested to learn that this latest version of the acoustic tweezer device requires about five hours to identify the CTCs in a sample of blood

Medical laboratory leaders and pathologists are well aware that circulating tumor cells (CTCs) released by primary tumors into the bloodstream are fragile and easily damaged. Many studies have sought to find ways to separate CTCs from surrounding cells. Such a process could then be used as an early-detection biomarker to detect cancer from a sample of blood.

One team of researchers believe it has a way to accomplish this. These researchers are using sound waves to gently detect and isolate CTCs in blood samples. In turn, this could make it possible to diagnose cancer using “liquid biopsies” as opposed to invasive conventional biopsies.

Researchers from Carnegie Mellon University (CMU) in collaboration with researchers from the Massachusetts Institute of Technology (MIT) and Pennsylvania State University (Penn State) have developed a method for using acoustic tweezers and sound waves to separate blood-borne cancer cells from white blood cells. The research team believes this new device could one day replace invasive biopsies, according to a CMU article. (more…)

New studies in UK and at Stanford University Show Lung Cancer Cells Circulating in Blood; Findings Could Make it Possible for Pathologists to Diagnose Cancer with ‘Liquid Biopsies’

Researchers at two different universities find circulating tumor cells in blood specimens and suggest that CTCs might be incorporated into medical laboratory tests for detecting cancer

One goal of many research initiatives is to develop a clinical laboratory test which can detect circulating tumor cells (CTC) in blood. This would be a less invasive method for testing and it is hoped such a test could detect cancer at a much earlier stage, when treatment can be much more successful.

Much effort is being put into developing what pathologists call a “liquid biopsy.” Recently, researchers at The University of Manchester in the United Kingdom (UK) and at Stanford University in the United States each published articles in Nature Medicine offering compelling data about the role blood tests could play in the diagnosis and treatment of lung cancer. (more…)

Genentech Scientists Zero in on “Liquid Biopsies” as a Way to Replace Tissue Biopsies in Breast Cancer

Surgical pathologists could gain new tool to diagnose many types of cancers


It might soon be possible to determine the HER2 status of breast cancer patients from blood samples rather than tissue biopsies. If this new technology proves feasible, it would give surgical pathologists and medical laboratories a different, and possibly less complex, methodology to use when assessing a case of breast cancer.

In its report about the study, Medscape Medical News, wrote that “HER2 status derived from circulating tumor cells (CTCs) from breast cancer patients was generally concordant with that derived from tumor tissue” and that “CTCs could prove to be an alternative to biopsies for assessing tumor tissue for biomarker status.”

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