Findings could lead to one-two-punch therapy to fight most common gynecologic cancer.
Modulating the hormonal environment in which endometrial cancers grow could make tumors significantly more sensitive to a new class of drugs known as PARP inhibitors, UCLA researchers have shown for the first time.
The findings could lead to a novel one-two–punch therapy to fight endometrial cancers and provide an alternative to conventional treatments, which, particularly with advanced disease, have limited efficacy. Endometrial cancer, which starts in the inner lining of the uterus, is the most common gynecologic cancer in the United States.
Studies on endometrial cancer cell lines have shown that PARP inhibition induces cell death when the tumor-suppressor gene PTEN is missing — a defect found in about 80 percent of human endometrial cancers.
However, the UCLA researchers wanted to test the inhibitors in a laboratory model with a tumor microenvironment that closely resembled human endometrial cancer to see if this therapy would be effective, said senior study author Dr. Sanaz Memarzadeh, an assistant professor of obstetrics and gynecology and director of the G.O. Discovery Lab at UCLA.
The findings are published today (Nov. 12) in Molecular Cancer Therapeutics, a peer-reviewed journal of the American Association for Cancer Research.
“A PARP inhibitor was given orally in two hormonal extremes — high and low estrogen,” Memarzadeh said. “The treatment achieved a significant reduction in tumor size in a low estrogenic milieu. In striking contrast, no response to the inhibitor was seen in tumors exposed to high levels of estrogen.”