Clinical OMICS

MAY-JUN 2019

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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www.clinicalomics.com May/June 2019 Clinical OMICs 21 In addition, Andrew Lane, Ph.D., professor at the Uni- versity of Kentucky College of Medicine, asserts that using the metabolomics approach for the purpose of diagnosis, but also prognosis and monitoring response to interven- tion, "relies very heavily on statistical analysis." He added that effect sizes are frequently quite small when looking for a few metabolites out of thousands in blood, which has been in contact with every part of the organism. Although numerous claims for high-accuracy biomarkers have been made, noted Lane, to date none of them have been shown to be robust. "Engaging scientists from multiple disciplines, including from biostatistics, computational science, analytical chem- istry, and engineering, is leading to significant achieve- ments in developing new tools that can be used to address challenges within the field," added Laurie Littlepage, Ph.D., assistant professor of cancer research, University of Notre Dame. In order to answer the big research questions, associat- ing a measurement with a biochemical pathway or a fun- damental mechanistic function relies on deciphering and understanding the complexity of the metabolic pathways of human physiology. "We need to try to get a metabolic map," noted Subramaniam. This is the big challenge for the coming decade—to understand the complete human metabolome. But, he added, that the pieces are starting to fall into place. Going where genomics cannot Targeting events that are an "Achilles heel" for cancer cells is how the University of Kentucky's Fan is pioneering metabolomics in cancer. Using 3D cultures from patient-de- rived organoids, Fan tests how individual patients respond to different drugs. Using 96-well plates, the Fan lab grows the organoids to which a tracer can be added to track the metabolism in the presence of a drug. Upon quenching the metabolism, they then measure the cell's response to the drug metabolically using both NMR and MS. In the end, they are trying to understand the mechanism of how the drug impacts the cancer cell through metabolism. Fan is pioneering research that will someday help patients receiving immunotherapeutics. Fan said that one of the powerful aspects to using metabolomics is harnessed with the plasticity of the immune system in patients. This is especially true with immunotherapy, where the efficacy can be dictated by the tumor microenvironment. For example, if the macrophage prevents the T cell from getting to the (continued on next page) The Tools of the Trade In the last decade, mass spectrometry has become orders of magnitudes better, and has changed the landscape dramatically, notes Shankar Subramaniam, Ph.D., chair and professor of Bioen- gineering University of California, San Diego School of Medicine. Scott Kuzdzal, Ph.D., vice president of marketing of Shimadzu Scientific Instruments, agrees. He told Clinical OMICs that "greater mass accuracy stability and ease of use of Quadrupole Time-of- Flight (QTOF) and triple quad mass spectrometers have opened up metabolomics to the masses." Not only that, but the synergy of different technologies or methods (e.g. liquid chromatography— mass spectrometry (LCMS) and gas chromatography—mass spec- trometry (GCMS) or targeted and non-targeted approaches) has increased. Lastly, software platforms have become unified and a single informatics platform such as Shimadzu LabSolutions can be used across many different instrument types. Some might suggest that depending on the specifics of the experiment—for example whether more specificity or higher res- olution are desired—different mass spec platforms should be em- ployed. For routine clinical laboratory use, Thermo Fisher notes that it has spent a decade working on a clinical mass spec solu- tion. Pete Van Overwalle, senior manager of market development at Thermo, said that the Cascadion SM Clinical Analyzer is the first all-in-one clinical analyzer with LC-MS/MS technology. The goal behind the fully automated Cascadion analyzer is to allow use by non-experts in a variety of settings, including within hospital lab- oratories for frequently ordered tests such as Vitamin D assays and immunosuppressant panels. Informatics platforms are also advancing by integrating mul- tiple 'omics datasets, including metabolomics, proteomics, flux- omics and transcriptomics. Kuzdzal points to "Garuda" (www. garuda-alliance.org) as an example of an open, communi- ty-driven, and common platform for systems biology and 'om- ics. With all of these recent advancements in MS technology, metabolomics researchers are better prepared than ever to an- swer the most complex questions about human cancer biology. —Julianna LeMieux, Ph.D. n Thermo Fisher's Cascadion clinical mass spec system debuted to much fanfare in 2017.

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