A new University of Michigan Medical School study sheds light on cell defects that lead to one common type of ovarian cancer and puts forth a promising new mouse model that already is being used for preclinical drug testing.The study, published in the April issue of Cancer Cell, focuses on ovarian endometrioid adenocarcinoma, the second most common form of a baffling, deadly disease for which early detection methods and effective treatments have been elusive so far. The American Cancer Society estimates there will be 22,430 new cases of ovarian cancer and 15,280 deaths from the disease in the United States this year.The new mouse model developed in the U-M lab is based on molecular defects shown to be present in human ovarian tumor cells, says senior author Kathleen R.
“We need models to do preclinical testing of new drugs that target the specific molecular defects in a patient’s tumor cells,” says Cho, a professor of pathology and internal medicine at the U-M Medical School. Using the genetically engineered mice her lab developed, one preclinical study is already under way, testing an existing drug called Rapamycin. The lab’s mouse model can also be used to test new drug candidates that inhibit the cell-messaging systems defective in ovarian endometrioid adenocarcinoma.
Genes that are mutated in ovarian cancer, as in other cancers, result in the production of proteins that alter the normal function of signaling pathways in cells. Defects in these pathways can prevent the normal action of tumor suppressor genes and allow cancer to develop and grow.The researchers analyzed gene mutations and signaling pathway defects in human ovarian tumor cells, then created a strain of genetically engineered mice with the same defects to see if ovarian tumors would develop. In all of the mice altered to possess both pathway defects, ovarian tumors — similar in morphology and biological behavior to human ovarian endometrioid adenocarcinomas — rapidly developed and often metastasized.
Women and their doctors at present have no effective ways to detect ovarian cancer at an early, treatable stage. There are few if any early physical symptoms of ovarian cancer and no tests to detect cellular changes that might indicate precancerous lesions, as Pap smears do for cervical cancer. By the time a woman with ovarian cancer experiences symptoms, tumors are typically large and often metastatic.