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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32 Clinical OMICs May/June 2019 by Shahriar Koochekpour, M.D., Ph.D., and his colleagues when he worked at the Louisiana State University Health Sciences Center. In 2014, while at Roswell Park Cancer Institute, Koochekpour and his colleagues described the E006AA-hT cell line, a derivative of E006AA, as a model for highly tumorigenic prostate cancer in African-Americans. When asked about the potential misclassification of both cell lines, Koochekpour confirmed that the parental cell line was in fact misclassified from that start and he and his colleagues are currently publishing an Erratum in Prostate, where the cell line was first described in 2004. He explained, "New information has been obtained on the E006AA epithe- lial cell line. We now believe that this cell line is a subclone of the 786-O renal adenocarcinoma line from a white male." "The analyses presented in the 2004 article are original and accurate using the techniques and methodologies that were available at the time," he continued. "We had no rea- son to doubt that the line we cultured did not originate from an African-American prostate tumor. We now believe it may have been contaminated in its early passages with the 786-0 cell line before it was cryopreserved, as 786-0 cells were also studied in the collaborator lab from which this line originated." The gap widens The misclassification of E006AA-hT and E006AA is more than the loss of a couple cell lines. E006AA-hT was one of only two commercially available cell lines for Afri- can-American prostate cancer and now only one remains: MDA-PCa-2b, which the study reported carries 86 percent West African ancestry. "Now it becomes even harder in vitro to make any type of assessment about African-Americans and prostate cancer, with only one cell line commercially available," Kimbro noted. Without sufficient preclinical models for African-Ameri- cans with prostate cancer, the health disparities gap currently seen in prostate cancer for African-Americans could widen even further. According to a 2018 study, African-Americans with low-grade prostate cancer have twice the likelihood of dying compared with men of other races. Cell lines play a critical role in early drug development because they are used during drug screenings to identify drug candidates for later study in animal models and even- tually the clinic. Without racially diverse cell lines, drug screenings identify only drug candidates that work in the dominant population, failing to consider the unique tumor biology of minority races left out. "These kinds of early drug screens can have profound effects later on down the road in terms of how we design trials and select patient popula- tion," said Daniel George, M.D., medical oncologist, Duke University. "So it's really important that we get that right from the start." George explained that the lack of representation of Afri- can-American prostate cancer in the preclinical setting has created a disparity in how drug screenings are performed and therapies selected. Historically, he said, drugs have been developed based on a tumor type without considering a patient's racial variation. Numerous studies have shown that African-American men with prostate cancer respond differently to cancer treatments compared with white men, suggesting a difference in tumor biology. Given that prostate cancer is a heterogeneous disease, replacing the E006AA-hT cell line is just the first step. Many more African-American prostate cancer cell lines, as well as patient-derived xenograft models, are needed to ade- quately study the disease and attempt to close the health disparities gap. George explained that developing preclin- ical models for minority patients is an "important step in the right direction," but doing so is especially challenging for prostate cancer because the cancer cells grow only "very (continued from previous page) "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." —Rick Kittles, Ph.D. associate director, City of Hope Sean Kimbro, Ph.D., associate professor of biology at North Carolina Central University

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