Ovarian cancer is the most deadly cancer of the female reproductive system. While it may respond well initially to chemotherapy, it also often recurs, and can be deadly within six months.
Now, a stem-cell biologist at the University of Texas McGovern Medical School in Houston, Wa Xian, believes she may be on the verge of being able to prevent the recurrence of ovarian cancer. Xian was recruited in 2015 to the Center for Stem Cell and Regenerative Medicine from the University of Connecticut Health Center, with the help of a Rising Star Award from CPRIT.
Xian cultures ovarian cancer cells in her laboratory, and can clone single cells to study the diversity of different cancer cells inside a single tumor. She is interested in ovarian cancer’s so-called stem cells, including those that survive chemotherapy to repopulate a tumor. This resistant subset of cancer stem cells, she thinks, is responsible for recurrent disease that is often more aggressive and less amenable to drug treatment.
Doctors believed that patients acquired chemotherapy resistance during therapy, but Wa’s research shows that a small population of resistant cells is already present even in patients who haven’t yet had treatment. “This is a game-changer, because we can now identify and capture this highly resistant population without waiting for recurrent disease,” Wa says. “We can test these cells against all available drugs and find the optimal combination to rid individual patients of their cancer.”
Xian and her husband, CPRIT Scholar Frank McKeon, a stem-cell expert at the University of Houston, have cloned thousands of stem cells from ovarian patient tumors. Each clone represents a single cancer cell, multiplied into a colony of identical cells. And they may have as many as 100 cell lines from each patient.
They have found that each cloned cell line is different from every other, both genetically and epigenetically. “This is amazing, and is why cancer is so difficult to treat,” she says. “So the best strategy is to develop a way to kill all of the tumor cells from the beginning.”
Her methods will lead the way to personalized medicine, she says. Because the cells multiply so rapidly in culture, she believes they could clone tumor cells taken from a patient during initial surgery, and within one month, have enough stem cells to screen for drugs that would kill all of them.
A quick turnaround time is important, because many patients die within six months. So far, Xian and McKeon have already completed this screening library for several patients—although, heartbreakingly, not in time to save lives.
The clones that are resistant to standard chemotherapy, including combinations of taxol and carboplatin, she says, are also resistant to other drugs that are usually used for treating cancer. “But surprisingly, there are FDA-approved drugs that are not used for cancer, but they kill these clones!” she exclaims. “Nobody predicted that they could be useful for cancer!”
Xian hopes to advance her work into a Phase I clinical trial with physicians at the Texas Medical Center. She says the environment at TMC is unique, with so many basic scientists and clinical physicians interacting. “It really helps put my research in a larger context,” she says.
Xian received additional funding for her work from the Department of Defense Ovarian Cancer Academy, connecting her directly with other ovarian cancer researchers around the U.S.
Xian received her undergraduate degree in biochemistry from Nankai University in China, and her Ph.D. in molecular genetics from the University of Texas M.D. Anderson Cancer Center. She was a postdoctoral fellow at Baylor College of Medicine, a research associate at Harvard Medical School, and a principal investigator in Singapore, prior to joining the faculty at the University of Connecticut School of Medicine in 2012.
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