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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Page 23 of 51

22 Clinical OMICs November/December 2018 it comes to CTCs, the two types of cancer are more similar than one might think. "Blood-based detection of CTCs in melanoma works even better than we thought," he noted. Lucci said he is looking forward to the results of ongo- ing clinical trials, like the DETECT study, currently under- way in Europe, that is looking at the possibility of using HER2 expression in CTCs to guide treatment decisions. In the meantime, Lucci and his colleagues are looking at the use of CTC counts from sequential blood draws in order to determine what these counts reveal about which breast can- cer and melanoma patients will respond to treatment. "We have such a large volume of patients that we can realisti- cally accomplish this in the near future," he said. CTCs vs. ctDNA Despite these kinds of advancements, the truth is that CTCs are an incredibly rare component of a cancer patient's blood. A significant amount of research has shifted away from CTCs to circulating tumor DNA (ctDNA) thanks to improve- ments in the depth, accuracy, and cost of high-throughput, next-generation sequenc- ing technology. "You get to see just about every piece of DNA you had in your tube," said Amir Goldkorn, M.D., a prostate cancer researcher and associate professor of medicine at the University of Southern California's Keck School of Medicine (USC). Goldkorn was one of the authors of the 2016 Current Oncology Reports review on liquid biopsies in prostate cancer. "Now that you have this technology, some investigators prefer to avoid the complexities and difficulties of isolating the actual cancer cells, because analyzing the cell-free DNA can be technically more straightforward." However, there are compelling reasons to continue to study CTCs, said Goldkorn. CTCs still represent the entire content of the cancer cells that make up the primary tumor and metastases. "DNA is just one part of the profile, whereas CTCs are living cells that contain the entire com- plement of DNA, RNA, and protein." By definition, ctDNA is only a subset of tumor DNA, DNA fragments that were released from dying cells. The bottom line, Goldkorn said, is that researchers have yet to complete the kind of large, prospective, well-controlled studies needed to determine which approach, CTC-based technologies or ctDNA-based ones, best informs treatment decisions and improves clinical outcomes. "That's the kind of work that needs to be done." Multi-Parametric Tests That's exactly the kind of work Goldkorn is doing. He said the answer may be a multi-parametric approach to liquid biopsies that attempts to get various kinds of information from a single blood sample. "We want to see what we are learning from each type of data, to what degree they over- lap, and to what degree they provide unique information. We want to understand how to use these technologies to develop the best predictive and prognostic tools that we can use for our patients in a way that is efficient, inexpensive, and non-invasive." Goldkorn said his group is conducting pilot studies, in addition to large, prospective, multi-center trials. The goal for multi-parametric studies is to take differ- ent technologies, apply them in an integrated manner to a single sample of blood, and develop the workflows where results can be viewed in parallel. "What we have seen so far is that you get complimentary information. It's important to look at both CTCs and ctDNA," Goldkorn said. Researchers are also looking at RNA- and protein-based tests, as well as studying extracellular vesicles. Once these studies are done, they will lay the foundation for commercial assays. "We may find we need the CTCs because we want the counts and to look for (protein) variants, but we want the cell-free (continued from previous page) (continued on page 24) A circulating tumor cell found using Oncotype DX AR-V7 Nucleus Detect Nicolò Manaresi, Ph.D., Menarini Silicon Biosystems

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