Clinical OMICS

NOV-DEC 2018

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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24 Clinical OMICs November/December 2018 DNA data because they give us the best profile of tumor mutations." But Daniel Danila, M.D., is skeptical about the future of multi-parametric tests. "It's theoretically a great idea. Practically, we have a lot of research to go. Right now, the buffers you use in these tests are very different," said Danila, a medical oncologist at Memorial Sloan Kettering Cancer Center. Increasing Detection Sensitivity Danila's work focuses on improving CTC detection. To do that, many are investigating new ways of harvesting CTCs. In 2016, Danila and his colleagues published a paper in The Cancer Journal that showed that two detection methods, AdnaTest Assay and ddPCR analysis, both detected cancer cells in spiked samples of blood more often than CellSearch. AdnaTest correctly found CTCs in 62% of the samples, ddPCR detected cells in 69% and CellSearch had a 45% detection rate. "The ddPCR assay required the lowest blood volume, least on-site processing, and longest stability for batch processing," the researchers wrote. "We need increased sensitivity. It's hard to monitor our patients if we can't detect CTCs, which serve as surrogate markers for survival in many cancer types." Menarini Silicon Biosystems, the current makers of Cell- Search, is working on further developing its system, said Nicolò Manaresi, Ph.D., the company's chief scientific offi- cer. "CellSearch has a leading role in the field of CTC. This is because of the clear defini- tion of a context of use, stan- dardized reagents and degree of automation which many of the alternative technologies for CTC enrichment and enumeration still lack," Manaresi said. However, the company is not standing still. "We keep work- (continued from page 22) Using Malaria To Retrieve CTCs A group of researchers from Australia and Denmark believe they have developed a new method of harvesting circulating tumor cells (CTCs) that puts cancer diagnostics using liquid biopsies within reach. That's because the new technology, which is based on a malaria protein called VAR2, selectively binds nearly all can- cer cell types at all stages of the tumor cells' life cycle and improve existing enrichment methods. "The sensitivity and specificity is striking," said Ali Salanti, Ph.D., a professor in the Department of Immunology and Microbiology at the University of Copenhagen and co-author of a paper results published in the June 2018 issue of Nature Communications that describes the new method. It involves coating magnetic beads with a recombinant form of VAR2. "We have shown that we can capture as few as 3 cells and as many as 500 cells spiked into 5mL of blood." Today, most CTC retrieval methods bind epithelial cell adhe- sion molecules (EpCAMs) that are found on the surface of CTCs produced by certain types of cancers. The challenge, however, is that not all cancer types express EpCAM and, during metas- tasis, epithelial cells transform into can- cer-spreading mesenchymal cells that do not express EpCAMs. So, EpCAM-based methods are missing CTCs that are at dif- ferent, more deadly stages. "Our method captures CTCs irrespective of their Ep- CAM status without capturing any such cells in benign or healthy controls," Salan- ti said. Salanti and his colleagues had been working for years to understand the pa- thology of malaria in pregnant women while developing vaccines for the dis- ease. They discovered that VAR2 binds to oncofetal chondroitin sulfate (ofCS) that, "There are many things you can do with CTCs if you can get them out of a sample without damaging them." —Andrew Newland, founder and CEO, ANGLE plc The Partsortix system from ANGLE features a single-use cassette the size of a microscope slide to separate living CTCs from blood cells.

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