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Clinical Laboratories and Pathology Groups

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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.

Cancer Research at the University of Manchester

The data released by that UK-based team also may pave the way for “personalized medicine,” according to a news release issued by The University of Manchester. The research was carried out at Cancer Research UK’s Manchester Institute—part of the Manchester Cancer Research Centre.

Pathologists understand that the Holy Grail, so to speak, of cancer diagnostics is a blood specimen with circulating tumor cells (CTCs). These liquid biopsies can eliminate traditional biopsies, which are not only expensive but are invasive in ways that take an emotional and physical toll on patients.

The availability of liquid biopsies would be important to lung cancer, an aggressive disease with low survival rates. The National Cancer Institute at the National Institutes of Health estimates 224,210 cases of small cell lung cancer (SCLC) and non-small cell lung cancer in 2014. During 2014, 159,260 people will die from the disease.

Liquid biopsies could give pathologists a new way—and perhaps a better way—to care for patients by diagnosing and monitoring lung cancer earlier in its course.

Findings Suggest CTCs in Abundance in Lung Cancer Patients’ Blood

Most SCLC cases are inoperable. Biopsies to investigate them further are rarely obtainable, the UK study authors point out in their article in Nature Magazine.

But CTCs are “prevalent in SCLC and present a readily accessible liquid biopsy. These data demonstrate that CTC molecular analysis via serial blood sampling could facilitate delivery of personalized medicine for SCLC,” wrote the study authors from the University of Manchester.

The UK researchers analyzed six SCLC patients’ blood samples. They found that the number of CTCs for each patient was related to their survival. Patients with fewer CTCs in their blood lived longer, according to the news release, reported Laboratory Equipment News in its story about this study.

Lung Cancer Patients Tend to Have More CTCs in their Blood Samples

Another finding of this study was that SCLC patients have more CTCs in their blood samples, as compared to patients with other types of cancer.

As to the effect of chemotherapy drugs on SCLC, the researchers used cells from a patient’s blood to grow tumors in mice.  The mice responded the same way as each donor patient, reported Cancer Research UK in a press release.

“Access to sufficient tumor tissue is a major barrier to us fully understanding the biology of SCLC,” stated Professor Caroline Dive, who led the study at the Cancer Research UK’s Manchester Institute. “This liquid biopsy is straightforward and not invasive so can be easily repeated and will allow us to study the genetics of each lung cancer patient’s individual tumor.”

Pictured above is Professor Caroline Dive who led a new study at the Cancer Research UK’s Manchester Institute. It suggested that “liquid biopsies” could be used to track lung cancer patients’ response to treatment. (Photo copyright Cancer Research UK.)

Pictured above is Professor Caroline Dive who led a new study at the Cancer Research UK’s Manchester Institute. It suggested that “liquid biopsies” could be used to track lung cancer patients’ response to treatment. (Photo copyright Cancer Research UK.)

Stanford Research Reveals ctDNA Biomarker of Cancer

Meanwhile, research conducted at Stanford University School of Medicine also suggests a blood test could be enough to diagnose many types of solid tumors and monitor patients’ personal treatment, according to a news release issued by Stanford University.

Like the study at the University of Manchester, researchers at Stanford University investigated patients with non-small cell lung cancer. The Stanford researchers believe their highly-sensitive method to detect and quantify circulating tumor DNA (ctDNA) could be applicable to many types of cancer.

“Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive assessment of cancer burden, but existing ctDNA detection methods have insufficient sensitivity or patient coverage for broad clinical applicability,” wrote the Stanford researchers. Their study was published in Nature Magazine.

They call their technique CAPP-Seq (which stands for Cancer Personalized Profiling by deep Sequencing). It is sensitive enough to detect just one molecule of tumor DNA among 10,000 healthy DNA molecules, the news release stated.

Pictured above is Maximilian Diehn, M.D., Ph.D, assistant professor of radiation oncology at Stanford University. He was one of the authors of a study describing a technique sensitive enough to detect just one molecule of tumor DNA in a sea of 10,000 healthy molecules. (Photo copyright Stanford University)

Pictured above is Maximilian Diehn, M.D., Ph.D, assistant professor of radiation oncology at Stanford University. He was one of the authors of a study describing a technique sensitive enough to detect just one molecule of tumor DNA in a sea of 10,000 healthy molecules. (Photo copyright Stanford University)

Implications for Patient Care and Cost of Diagnosis and Treatment

What do the findings of these research programs mean to cancer patient care?

“It shows that circulating tumor DNA is a viable diagnostic test, not only for tracking mutations in advanced patients but possibly also for screening. I really think there is a future for this in cancer,” explained Luis Diaz, Jr., M.D., in a Medscape article on the Stanford research.

Diaz, who was not involved with the research, is affiliated with the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore.

Upcoming clinical trials may show whether CAPP-Seq improves patient outcomes, reduces costs and applies to other cancers.

In the meantime, in a story published by HealthLine News, the Stanford radiation oncologist told the publication that the team is establishing the CTC diagnostic test in the Stanford clinical laboratory for evaluation.

Using Liquid Biopsies to Watch Other Types of Cancers

Lung cancer is not the only cancer being watched by liquid biopsy research.

Dark Daily readers may recall past reports on liquid biopsy use for ovarian cancer in February and breast cancer in October 2010. (See Dark Daily “Harvard Researchers Create Chip-based ‘Liquid Biopsy’ Device That Offers a Novel Way to Monitor Treatment of Ovarian Cancer Patients and Only Costs $1” , February 14, 2014; and “Genetech Scientists Zero in on ‘Liquid Biopsies’ as a Way to Replace Tissue Biopsies in Breast Cancer” , October 13, 2010.)

It’s certainly an interesting time to be a pathologist or laboratory professional. Additional liquid biopsy technology advances will likely be published by respected research teams and others. These findings could eventually change the way some cancers are diagnosed and monitored by giving medical laboratories new diagnostic tests that are non-invasive and ultimately improve quality of life and survival for cancer patients.

—By Donna Marie Pocius

Related Information:

“Liquid Biopsy” Offers New Way to Track Lung Cancer

Tumorigenicity and Genetic Profiling of Circulating Tumor Cells in Small-Cell Lung Cancer

“Liquid Biopsy” Tracks Cancer

“Liquid” Lung Cancer Biopsies Will Speed-up Drug-Resistance Research

Blood Test Could Provide Rapid, Accurate Method of Detecting Solid Cancers, Study Finds

An Ultrasensitive Method for Quantitating Circulating Tumor DNA with Broad Patient Coverage

Ultrasensitive “Liquid Biopsy” May Detect Many Solid Tumors”

Simple Blood Test Could Diagnose Solid Cancers

Harvard Researchers Create Chip-Based “Liquid Biopsy” Device That Offers a Novel Way to Monitor Treatment of Ovarian Cancer Patients and Only Costs $1

Genetech Scientists Zero In On “Liquid Biopsies” As a Way to Replace Tissues Biopsies in Breast Cancer

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