UCLA researchers continue to make advances in the field of nanotechnology. Their latest breakthrough is an improved method for capturing and analyzing cancer cells that break away from patients’ tumors and circulate in the blood. The researchers note that with the improvements, even single cancer cells can be accurately detected and safely isolated from patient blood samples for continuous analysis. The study was published online on February 22 in the peer-reviewed journal Angewandte Chemie; it will be featured on the cover of the March 2013 issue of the journal.
The cancer cells, called circulating tumor cells (CTCs), metastasize or spread from one tumor to other parts of the body and form new tumors. When they are isolated from the patient’s blood early over the course of disease progression, they can provide physicians with critical information about the type of cancer, the characteristics of the individual cancer, and its possible progression. These cells can also provide information regarding how to design a personalized treatment approach for a specific patient.
In recent years, a UCLA research team led by Hsian-Rong Tseng, associate professor of molecular and medical pharmacology at the Crump Institute for Molecular Imaging and a member of the California NanoSystems Institute and the Jonsson Comprehensive Cancer Center (JCCC) has developed a “NanoVelcro” chip. Blood is passed through the chip, in which very small nanoscale hairs (nanowires or nanofibers) coated with protein molecules from the immune system (antibodies) that match proteins on the surface of cancer cells trap CTCs and isolate them for further studies. The researchers note that the CTCs trapped by the chip also act as a “liquid biopsy” of the tumor, providing convenient access to tumor cells, and earlier access to potentially fatal metastases. This study of the microscopic structure of diseased tissue is called histopathology analysis of biopsy samples and is considered to be the “gold standard” for determining tumor status. Being able to extract viable cells allows detailed analysis of the type of cancer, and the various genetic characteristics of that patient’s specific cancer.
The researchers have made an improvement in the chip by replacing the original non-transparent silicon nanowire substrate inside the device. These nanowires seize the cancer cells as the blood passes by them. Using a new type of transparent polymer nanofiber-deposited substrate, Tseng and his colleagues were able to “pick” single CTCs immobilized on the transparent substrates by using a miniaturized laser beam knife, a technique called laser microdissection (LMD). “This paper summarizes a major milestone in the continuous development of NanoVelcro assays pioneered by our research group,” explained Dr. Tseng. He added, “We now can not only capture cancer cells from blood with high efficiency, but also hand pick single CTCs for in-depth characterization to provide crucial information that helps doctors make better decisions.”
Using the new assay on patients’ blood that contained circulating melanoma cells (CMCs), the researchers were able to isolate and preserve single CMCs. Melanoma is a deadly type of skin cancer that is prone to spreading quickly throughout the body. The ability to capture and preserve single CMCs allows physicians to analyze the DNA structure of the cells and determine genetic characteristics of the patient’s cancer, confirming that the circulating cells remained genetically similar to the tumor they came from.
The preservation of single captured CMCs in the proof-of-concept study also allowed researchers to conduct an analysis, called single-cell genotyping, to find within the cell a specific target (BRAFV600E) for a drug called vemurafenib. This designation describes a mutation in a protein called BRAF that appears in approximately 60 percent of melanoma cases. Drugs that inhibit BRAF are able to slow and often reverse the growth of melanoma tumors.
“With this technology we are getting closer to the goal of a widely clinically applicable liquid biopsy, where we can sample cancer cells by a simple blood draw and understand the genes that allow them to grow,” said Dr. Antoni Ribas, professor of medicine in the division of hematology-oncology and JCCC member, and one of Tseng’s key collaborators. “With the NanoVelcro chips we will be able to better personalize the treatments to patients by giving the right treatment to stop what makes that particular cancer grow.”
Dr. Roger Lo, member of Dr. Tseng’s team and an assistant professor in the department of medicine, division of dermatology and department of molecular and medical pharmacology, and JCCC member, added, “This scientific advancement — being able to capture the melanoma cells in transit in the blood and then perform genetic analysis on them — will in principle allow us to track the genomic evolution of melanoma under BRAF inhibitor therapy and understand better the development of drug resistance.”