TGen and Washington University researchers discover new approach to treating endometrial cancer
Inhibitor turns 'off' receptors; stops the growth of endometrial tumors and kills cancer cells
Researchers at the Translational genomics Research Institute (TGen) announced a new approach to treating endometrial cancer patients that not only stops the growth of tumors, but kills the cancer cells. In a potentially major breakthrough, TGen scientists and collaborators at Washington University School of medicine in St. Louis discovered that introducing a particular inhibitor drug can turn "off'' receptors responsible for the growth of tumors in a significant number of patients with endometrial cancer. And, they found that the inhibitor drug proved effective even in cancer tumors containing a commonly occurring mutant gene, PTEN, previously associated with resistance to drug treatment. TGen's findings appear in Cancer Research. A clinical trial based on the TGen study will start within the next year.
Dr. Pamela Pollock, an associate investigator in TGen's Cancer and Cell Biology Division and the paper's senior author, led a team that used the latest genome-scanning technology to sequence 116 endometrioid endometrial tumor samples. This work was done in association with Dr. Paul Goodfellow, an expert in endometrial cancer and a professor in the departments of Surgery and of Obstetrics and Gynecology at Washington University.
Pollock and colleagues in May 2007 announced that they had discovered previously unrecognized alterations in the fibroblast growth factor receptor 2 (FGFR2) gene. The altered FGFR2 is present in the cancer cells of nearly 15 percent of women with endometrioid endometrial tumors. These kinds of tumors represent 80 percent of all endometrial cancers.
By introducing a commercially available inhibitor drug, PD173074, TGen researchers showed that they could stop the growth of tumors, and even kill cancer cells, in cases where the tumors contained the altered FGFR2 gene. The altered gene causes the receptors to get stuck in the "on'' position and signal the endometrial cells to grow out of control.
"These findings could accelerate the development of new treatments for endometrial cancer because there are already drugs in clinical trials that inhibit FGFR2 function,'' Pollock said.
Pollock plans to start clinical trials with an FGFR inhibitor in endometrial cancer patients within a year. The trials will be conducted in collaboration with Dr. Matthew Powell, a gynecologic oncologist and assistant professor of Obstetrics and Gynecology at Washington University School of Medicine.
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