Cervical Cancer Treated in Mice with FDA Approved Drugs
According to the National Cancer Institute it is estimated there will be 11,270 new cervical cancer cases and 4,070 deaths in the United States in 2009. Around the world this number can be 500,000 new cases each year with half not surviving. Treatment of cervical cancer depends on the stage, but can involve surgery, radiation, and chemotherapy.
This week’s (Nov. 9) Proceedings of the National Academy of Sciences includes news on research using two FDA-approved drugs used to treat breast cancer and osteoporosis. Researchers at the University of Wisconsin-Madison School of Medicine and Public Health have eliminated cervical cancer in mice using fulvestrant and raloxifene.
Cervical cancer forms in tissues of the cervix (the organ connecting the uterus and vagina) and is usually a slow-growing cancer that may not have symptoms. Cervical cancers can be found with regular Pap tests. Cervical cancer is almost always caused by human papillomavirus (HPV) infection.
Paul Lambert, of the McArdle Laboratory for Cancer Research and the UW-Madison Carbone Cancer Center and colleagues use special mice they developed more than 20 years ago to study cervical cancer. The mice were genetically engineered to carry human papillomavirus (HPV) 16, known to be strongly associated with cervical cancer.
“Since the cervix and other female reproductive organs are so responsive to estrogen, our lab and others began to focus on that hormone," Lambert says.
Sang-Hyuk Chung, a postdoctoral fellow in Lambert's lab, zeroed in on one of the two receptors that mediate estrogen function in cells - estrogen receptor (ER) alpha. He crossed his HPV mice with mice in which ER alpha had been knocked out, then gave the animals estrogen. When the mice didn't develop cervical cancer or even precancerous lesions, Chung knew that ER alpha was an essential player in the slow cancerous process.
Chung turned to an ER alpha blocker used to treat breast cancer, fulvestrant, and tested it on the HPV-positive mice with cervical cancer. After one month, he found that 11 of 13 mice lost all signs of cancer. But cancer remained in all the control mice that hadn't gotten the drug.
Chung then tested a second drug, raloxifene, which is used to treat breast cancer and osteoporosis, to make sure that the first results weren't a fluke. He found the same strong, blocking effect.
Finally, the researchers gave the drugs to animals with the precancerous lesions and found that the ER alpha blockers prevented the lesions from progressing to cancer.
Lambert's team is now testing human cervical cancer cell lines to see if ER alpha blockers stop the growth of the malignant cells. The next step will be to test the drugs on tissue samples removed from women following surgery for the cervical cancer.
"We can't be sure how the science will translate from animals to humans," says Lambert, "but we have faith in our mouse model. There are many similarities in how cervical cancer develops and manifests itself in women and in mice."
The lab studies, which should take one or two years to complete, could be followed quickly with phase-two or phase-three clinical trials. Early phase trials would not be necessary since the drugs have already been approved for clinical use.