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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Page 34 of 50 May/June 2019 Clinical OMICs 33 rarely" once implanted into an animal or other site. "That just means we need to develop more efficient mechanisms to grow those cells or we need to do it in greater numbers to show that even with that low efficiency, some models survive," he said. Lasting effects Cell line misclassifications not only set back research, but even once the misclassification is known and accepted by the scientific community, the misinformation can linger in the literature. For example, in 2007, the MDA-MB-435 cell line, which was derived from a female breast cancer patient in 1976, was shown to no longer be breast cancer but in fact of melanoma origin. "It was, at the time, the only cell line we had that was metastatic," recalled James Rae, Ph.D., associate professor of pharmacology, University of Michigan, who was the pri- mary author on the 2007 study. "People that were study- ing metastasis, they were relying on this cell line for their model, and when it came up that it's not breast and it's mel- anoma, people weren't all that crazy." With time, the breast cancer community accepted the evidence that the MDA-MB-435 cell line was not breast cancer, but the community is still feeling lasting effects, as researchers unknowingly continue to use the cell line as a model for breast cancer. "You'll still see to this day that people are publishing papers using this as a model for breast cancer," Rae said. In 2014, researchers published work showing that at least 36 peer-reviewed studies used the MDA-MB-435 cell line as a model for breast cancer. As to why the MDA-MB-435 cell line is still being mis- taken as a breast cancer model, Rae reasons that researchers from other fields who are not familiar with breast cancer may read a journal article from the early 2000s and conclude that the cell line is a breast cancer model. "In science you've got to learn to read the literature and you got to learn to be skeptical and you've got to learn to do your fact-checking," said Rae. "You would think scientists would be quick to correct things once it's in the literature, but that's not the case all the time," said Kittles about the continued use of the MDA-MB-435 cell line as a breast cancer model. "I used to say that many scientists were very fickle and they jump on new trends really quickly, but in some cases, there's a lot of scientists that just won't budge, and as long as nobody calls them out on it, they'll continue to do it." Building Preclinical Breast Cancer Models for All For nearly fifteen years, Michael Lewis, Ph.D., professor at Baylor College of Medicine, has been collaborating with his colleagues to create patient-derived xenograft (PDX) breast cancer models. Baylor College of Medicine is a member the PDX Development and Trial Centers Research Network, which the National Cancer Institutes launched in 2017 to accelerate translational research. Now, Lewis and his colleagues have more than 70 breast cancer models at Baylor that represent the diverse patient population the institution serves, with approximately half being of Hispan- ic origin, a quarter African-American, and a quarter Caucasian. James Rae, Ph.D., associate professor of pharmacology, University of Michigan, said that Lewis makes the models "readily available to all of us in the community" and that they are "a great resource." The purpose of the models is to essentially replace patients in early-stage drug development and help identify which drugs should move into clinic, Lewis explained. "We've shown that a lot of the biology of the tumor of origin is recapitulated in the PDX, including genomics, transcriptomics, proteomics, histology, and biomarkers. Those kinds of things don't change when you take the tumor from people and put them into mice," he said. "We can demonstrate that whatever grows, arose from the tumor that we transplanted because we can do genetic fingerprinting, and then we follow it over time and make sure that that fingerprint doesn't change." To share these models with the research community, Lewis and his colleagues launched the PDX portal in April 2019. The PDX portal is a website that features dozens of PDX breast cancer models and the models are annotated with various demographic and clinical information, such as age, race, hormone receptor, and stage. "This will allow anybody in the world who has access to the Web to browse our collection of PDX models that we're able to make public," he said. —Christina Bennett n Confocal microscopy image of a metastatic estrogen receptor positive patient-derived xenograft genetically tagged to express green fluores- cent protein constitutively.

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