June 10, 2020
A nanochip created by researchers at The University of Kansas Cancer Center and the University of Kansas has the potential to detect and track breast cancer tumor progression and metastasis. The chip was able to detect early early-stage and metastatic tumors using plasma from 100 individuals. The findings from their study were published in Science Translational Medicine.
Ductal carcinoma in situ (DCIS) is considered the earliest stage of breast cancer. In DCIS, the cells lining the milk ducts of the breast have become cancerous, but they have not spread to surrounding breast tissue. When caught at this stage, the survival rate is greater than 99%. Less than half of people with DCIS progress to invasive breast cancer. Current early detection methods include breast self-exams, regular clinical breast exams and mammograms. These methods, particularly mammograms, are effective and have saved countless lives. But there are limitations, says lead author Yong Zeng, PhD, a chemist, biomedical engineer and member of the cancer center.
“Mammographic imaging has dramatically changed the landscape of how we detect breast cancer. However, it does not capture the number of cancer cells or tumor size. A diagnosis of DCIS does not mean a person will develop invasive breast cancer. They may not require any further treatment and can rely instead on surveillance,” said Dr. Zeng.
Those with invasive breast cancer, he added, must be closely monitored for metastasis, or spread, of their cancer. Between 20 and 30% of all breast cancer cases will progress to metastatic disease. Long-term observation of cancerous or pre-cancerous tumors is crucial, but conventional tissue biopsies are invasive, painful and costly. Furthermore, there are no tools to monitor when cancer starts spreading from its original site. Recognizing this unmet need, Dr. Zeng partnered with cancer biologist and cancer center member Liang Xu, MD, PhD, to develop a convenient, cost-effective way to track disease progression.
“We wanted to develop a liquid biopsy method that is less invasive and easier on the patient,” Dr. Xu said. “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.”
Based on the exosome analysis nanochip created in Dr. Zeng’s lab, they developed a new liquid biopsy tool. Instead of surgery, the patient undergoes a simple and non-invasive blood draw, a “liquid biopsy,” and the fluid is piped on to the chip. About the size of a stick of chewing gum, the chip contains three-dimensional micropatterns and channels to enhance the detection of cancer biomarkers. The tool is made using a high-resolution inkjet printer in Dr. Zeng’s lab.
“Exosomes, which are extracellular vesicles that are released from cells, are an important player in cell functions and diseases via transporting molecular information between cells,” Dr. Zeng said. “While all cells produce exosomes, tumor cells produce more aggressively than most, making them a promising target for cancer diagnosis via liquid biopsy. Using the lab-on-a-chip, it is possible to obtain a comprehensive tumor profile to more accurately monitor a patient’s disease burden and progression in real-time.”
Current lab-on-a-chip devices have primarily focused on measuring the expression of biological molecules in extracellular vesicles. The novel chip is designed to measure both exosomes’ molecular composition and their enzymatic activity that is critical for tumor invasion and metastasis. The ultrasensitive chip reveals this activity even at very low concentrations when the tumor is in its earliest stages.
The team will utilize this new tool in an ongoing lung cancer clinical trial at KUCC and are obtaining funding for a clinical trial for breast cancer patients.
“Our team is applying this technology to address unmet needs in cancer medicine,” Dr. Zeng said. “Together, spanning biology, chemistry, engineering and clinical disciplines, we are moving this technology from bench to bedside.”