Researchers have found a potential new approach to treating endometrial cancer — a drug that was shown to be effective even against human endometrial cancer cell lines that tend to be treatment resistant.
Scientists at the School of Medicine and at the Phoenix-based nonprofit research organization Translational Genomics Research Institute (TGen) discovered that introducing a particular inhibitor drug can turn off cell receptors that are responsible for tumor growth in a significant number of patients with endometrial cancer.
The inhibitor drug proved effective even in endometrial cancer cell lines containing a commonly occurring mutant gene, PTEN, previously associated with resistance to drug treatment.
The findings appeared Sept. 2 in a paper published as a priority report by the journal Cancer Research.
Endometrial cancer, which invades the inner wall of the uterus, is the most common gynecological cancer in the United States. This year more than 40,000 women will be diagnosed, and nearly 7,500 women will die of the disease, according to the American Cancer Society (ACS).
Among women, only breast, lung and colon cancers strike with more frequency. And while endometrial cancer is slow to develop and often not detected until after age 60, nearly one in eight women who are diagnosed die within five years, according to the ACS.
Pamela Pollock, Ph.D., an associate investigator at TGen and the paper’s senior author, led a team that used the latest genome-scanning technology to sequence 116 endometrioid endometrial tumor samples. The work was done in association with Paul Goodfellow, Ph.D., an expert in endometrial cancer and co-director of the Hereditary Cancer Core at the Siteman Cancer Center.
In May 2007, the research team 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, a kind of tumor that represents 80 percent of all endometrial cancers.
By introducing a commercially available inhibitor drug, PD173074, the researchers showed that they could stop cell growth and induce cell death in endometrial cell lines that contained the altered FGFR2 gene, which causes cell receptors to get stuck in the “on” position and signal endometrial cells to grow out of control.
Treatment of endometrial cancer can involve surgical removal of the uterus, radiation and chemotherapy. While many women are successfully treated with these approaches, about 15 percent of those with endometrioid endometrial cancer have persistent or recurring tumors that are resistant to current drug therapies. Mutations in several genes previously have been identified in endometrial tumors, but none have been suitable drug targets — until now.
“This targeted approach holds great promise for patients with uterine cancer (endometrioid endometrial) tumors that contain the FGFR2 mutation and offers yet another powerful example of how genomic medicine is changing the way we look at and treat cancer,” said Daniel Von Hoff, M.D., TGen’s physician-in-chief.
Goodfellow, also a professor of surgery and of obstetrics and gynecology at the School of Medicine, agreed, saying that the discovery that endometrial cancer cells die when treated with an FGFR2 inhibitor — even when they carry other genetic abnormalities common in uterine cancers — suggests anti-FGFR2 therapies have great potential.
A clinical trial based on the study is planned for next year.