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Liquid Biopsy Tool Can Detect Breast Cancer in Earliest Stages

Liquid Biopsy Tool Can Detect Breast Cancer in Earliest Stages
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Published on July 28, 2020

Lab-on-a-Chip Can Detect Breast Cancer With Simple Blood Draw

An ultrasensitive diagnostic device was able to detect early-stage and advanced breast cancer cases simply by testing a patient’s blood, a finding which could lead to earlier diagnosis and interventions and better outcomes for patients.

The “lab-on-a-chip” called EV-CLUE detected early-stage cancers and metastatic tumors using plasma from 100 individuals. The chip was created by researchers at the University of Kansas Cancer Center and the University of Kansas. Their findings were published in June in Science Translational Medicine.

Using a Blood Sample to Detect Cancer Cells

“We wanted to develop a liquid biopsy method that is less invasive and easier on the patient,” said Dr. Liang Xu, co-researcher and a professor of molecular bioscience at the University of Kansas, in a press release. “Fluids in our body, including blood and plasma, contain rich data providing clues to our health. Cancerous tumor cells can be spotted long before being detected by a tumor biopsy.”

In a group of 30 patients, EV-CLUE was able to tell the difference between healthy samples and cancerous samples 96.7 percent of the time. In a larger test involving 70 patients, EV-CLUE’s success rate was 92.9 percent.

The research team developed EV-CLUE using a high-resolution inkjet printer. The patient undergoes a simple blood draw and the fluid is piped on to the chip to perform the biopsy.

The chip, which is about the size of a stick of chewing gum, is based on the exosome analysis nanochip that was created in lead author Dr. Yong Zeng’s lab. It contains three-dimensional micropatterns and channels to enhance the detection of cancer biomarkers.

“Exosomes, which are extracellular vesicles (EV) that are released from cells, are an important player in cell functions and diseases via transporting molecular information between cells,” said Dr. Zeng, a chemist, biomedical engineer, and member of the cancer center.

“While all cells produce exosomes, tumor cells produce more aggressively than most, making them a promising target for cancer diagnosis via liquid biopsy.”

Challenges of Using Blood Tests for Early Detection

Researchers around the world have been working on a liquid biopsy tool for years. While progress has been made, many challenges remain, Dr. Zeng said in an email to Patient Power. For example, he said the level of biomarkers released from small tumors at early stages could be present at extremely low concentrations in blood.

“Therefore, it creates significant challenges for detecting these early-stage biomarkers with clinically meaningful sensitivity and specificity,” he said.

He said in the case of EVs, the clinical study of EV-associated markers for cancer has been largely hindered by the challenges associated with isolating and distinguishing tumor-derived EVs from host cell EVs in bodily fluids.

“Moving liquid biology tools towards clinical utilities calls for breakthroughs in both biological studies and technology innovations,” Dr. Zeng said.      

Unlike other chips, EV-CLUE is designed to measure both exosomes’ molecular composition and their enzymatic activity that is critical for tumor invasion and metastasis. It can detect this activity even at very low concentrations when the tumor is in its earliest stages, Dr. Zeng said.

Complementary Diagnostic Tools to Improve Breast Cancer Treatment

The average five-year survival rate for women with localized breast cancer is 99%, according to the American Cancer Society. Less than half of people with ductal carcinoma in situ (DCIS), the earliest stage of breast cancer, progress to invasive breast cancer.

While early detection methods, particularly regular mammograms, are effective and have saved lives, there are limitations, Dr. Zeng said. For example, mammographic imaging does not provide much molecular information about the tumors nor predict the risk of the cancer developing into invasive and even metastatic disease.

Long-term observation of cancerous or pre-cancerous tumors is critical, but tissue biopsies are invasive and can be painful and costly. Furthermore, there are no tools to monitor when cancer starts spreading from its original site. 

“A diagnosis of DCIS does not necessarily mean the future development of invasive breast cancer and may not require any further treatment that is expensive and painful for patients,” Dr. Zeng said. “Our chip-based strategy could provide a complementary test to the imaging for a periodic check-up to monitor the progression of tumors and help clinical decision-making.”

Researchers are currently using EV-CLUE in an ongoing lung cancer trial at the cancer center and are obtaining funding for a clinical trial for breast cancer patients.

~Megan Trusdell


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