New Liquid Biopsy Tackles Early Cancer Detection via Cell Clusters

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Liquid biopsies, or testing for tumor cells or DNA circulating in the blood stream, has become an increasingly viable option for detecting certain forms of cancer.  A new international study on the latest liquid biopsy technology published data that shows it is possible to detect several types of cancer via one blood test, often before the patient is symptomatic.

Liquid biopsies have appealing aspects for clinicians compared to other means of cancer detection. It is non-intrusive and presents no real risk to the patient, compared to other methods of cancer detection such as biopsies or various imaging modalities, both of which rely on being able to visualize a tumor in order to estimate the extent of disease progression.

One drawback of previous liquid biopsies was that the assay was not specific to different cancer types, and biomarkers for all known cancer types are not yet know.

Now, however, a coalition of scientists from India, the United States, and the United Kingdom has published a study suggesting there is clinical evidence for an innovative liquid biopsy assay which can detect clusters of any type of cancer cell in the blood of asymptomatic individuals. The researchers have developed this assay as a non-invasive screening and diagnostic test, which could make cancer screening easier, efficient and affordable, not to mention a welcome breakthrough in cancer detection and diagnosis.

The researchers for this study believe their liquid biopsy will soon be available commercially.

Principal author Dr. Dadasaheb Akolkar, who is the research director at Datar Cancer Genetics, said, “This is the first study of its kind to investigate the prevalence of circulating tumor emboli or C-ETACs (Circulating Ensembles of Tumor Associated Cells), in a population size cohort of over 16,000 participants, to establish a definitive new systemic hallmark of cancer.”

The authors have stated, “Ubiquitous C‐ETACs qualify as a systemic hallmark of cancer and their presence in an individual’s blood is the colloquial ‘smoking gun’—the absolute and direct evidence of viable neoplastic disease.”

Early detection of cancer is crucial but challenging, because current methods of cancer detection lack efficient and reliable screening methods.  Many patients at high risk for developing certain types of cancer – such as individuals with a family history, who carry specific genetic mutations for that disease, or who have previously had cancer – choose to screen themselves on a regular basis for any sign of cancer development, so that they may give themselves the best chance of beating it should it ever occur.  Current methods may likely give them a false negative result, in that scientists must wait for a tumor to become large enough to visualize before they can give a diagnosis or perform any additional molecular tests, which is clearly an imperfect method.

Most of these commercially available cancer-screening tests are invasive and expensive, and  currently available cancer screening techniques such as mammograms and low-dose CT scans (LDCT) carry additional radiation risks. Colonoscopies are invasive, blood based markers are non-specific and tissue biopsies for diagnosis have the same risks as general surgical procedures.

“The technique we have used is a breakthrough innovation,” Akolkar said.  “When clusters of cells break off from an early stage tumor and enter the bloodstream we can efficiently and accurately isolate a few hundred malignant cells from more than 100 million cells, from just 10 mL of blood. While almost all the cancer samples had these cell clusters, they were seen in very few of the samples which were apparently without cancer.”

Speaking on the breakthrough study and technique, Rajan Datar, chairman and managing director of Datar Cancer Genetics where the assay was developed, said, “Cancer is rapidly becoming a civilizational challenge. Importantly, cancer deaths are mainly due to late detection. We believe that this innovative blood based test is a breakthrough in cancer screening and will impact outcomes by easy, patient-friendly detection and diagnosis in apparently healthy people who may have a silent malignancy in their bodies! It has the potential to eliminate the need for invasive biopsies and the risks associated with it. In the near future, a simple, inexpensive blood test that could be all that is required to reliably detect and diagnose cancer, even before any symptoms are seen.”

This first study involved 16,134 participants, including 5,509 patients with cancer (from the TrueBlood study) and 10,625 individuals with no symptoms (from the RESOLUTE study); this new liquid biopsy test has shown an accuracy of more than 94%, an impressive feat. The C-ETACs were seen in 89.8% of cancer cases and in only 3% of apparently healthy, asymptomatic individuals who had no abnormal findings in presently used screening tests. The study was the largest of its kind in the world.

Enumeration of C‐ETACs is presently a cumbersome and laborious manual process which is why it has only been attempted only in a single subcohort, but the authors plan to further develop and refine their methods to enable quantitative correlation of C‐ETACs with treatment status, radiological findings and extent of disease.

Datar Cancer Genetics presented further data on their results at several leading international conferences including AACR, ASCO and ESMO, annual cancer conferences that present oncologists with the latest breakthroughs in cancer research.   It will be very interesting to see how this liquid biopsy fares if and perhaps when it becomes mainstream, particular in detecting notoriously hard to detect cancers.

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