A team of researchers may have eliminated a significant stumbling block in cancer research—the inability to sustain both normal and cancerous cells in the lab without altering their genetic material—with a lab technique that could accelerate biomedical research and personalized medicine (Am J Pathol 2012;180:599–607).
“Because every tumor is unique, this advance will make it possible for an oncologist to find the therapies that kill a patient's cancer cells and spare normal cells,” explains Richard Schlegel, MD, PhD, the study's senior investigator and chairman of the department of pathology at the Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center.
Rather than prescribing a drug and waiting to see how the patient responds, Schlegel suggests, pathologists could grow the patient's cells in the lab, administer drugs to several different cultures either alone or in combinations, and determine which ones will likely be most effective. He says they could also test the cells to see if they develop resistance to a given agent.
Schlegel's colleagues, including Alison McBride, PhD, of the National Institute of Allergy and Infectious Diseases, and other researchers from Georgetown and the NIH, combined presenescent epithelial cells from a human breast tumor with irradiated fibroblast feeder cells and the Rho kinase (ROCK) inhibitor Y-27632. The cells rapidly reverted to a stem-like state and began to grow and divide. Using lung cells that were propagated in the same way, they showed that withdrawing the ROCK inhibitor forced the cells to differentiate into normal adult cells again.
The response with breast cells was so dramatic that the scientists decided to try the technique with prostate cancer cells, which are notoriously difficult to grow in the lab. “They took off like a rocket,” says Schlegel. The team also grew lung and colon cancer cells alongside normal cells. “In short, we discovered we can grow normal and tumor cells from the same patient forever,” he adds. Further tests showed that these “conditionally reprogrammed cells” also could be generated from cryopreserved human tissue. Additionally, because the researchers have generated cultures from as few as 4 cells, they plan to try growing cultures from circulating tumor cells.
Pancreatic adenocarcinoma cells, which are difficult to grow in vitro, prospered using the “conditionally reprogrammed cell” method. [Photo courtesy of Xuefeng Liu and Richard Schlegel, Georgetown University]
Pancreatic adenocarcinoma cells, which are difficult to grow in vitro, prospered using the “conditionally reprogrammed cell” method. [Photo courtesy of Xuefeng Liu and Richard Schlegel, Georgetown University]
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