UCLA researchers, for the first time have shown that 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.
The findings could lead to a novel one-two punch therapy to fight endometrial cancers and provide an alternative option for conventional treatments that, particularly in advanced disease, have limited efficacy.
Studies on endometrial cancer cell lines have shown that PARP inhibition induces cell death when tumor suppressor 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 resembles human endometrial cancer to see if this therapy would be effective, said study senior author Dr. Sanaz Memarzadeh, an assistant professor of obstetrics and gynecology and director of the G.O. Discovery Lab at UCLA.
"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."