Ovarian cancer is largely asymptomatic until it is at an advanced stage, and so is commonly first diagnosed at Stage 3 or 4---very late on the cancer spectrum. Of the roughly 22,000 women (half of whom are less than 63 years old) diagnosed every year in the U.S. with advanced ovarian cancer, 80% will eventually die from the disease. When detected at an early stage (i.e. Stage 0/1) ovarian cancer has a cure rate approaching 95%. Unfortunately, only about 15% of ovarian cancer cases are detected in the early stages. All early detection screening approaches attempted to date have been unsuccessful. Dr. Christian Barrett of the Frazer Lab in the Division of Genome Information Sciences at UC San Diego is developing a method that appears to be promising for the early detection of ovarian cancer. His approach is based on detecting a small number of cancerous cells in tissue samples that are collected from the cervix in standard Pap tests. The detection test is now entering a long-sought and exciting stage after many years of intense effort. With colleagues at the UC San Diego Moores Cancer Center Drs. Barrett and Frazer have initiated a clinical trial that intends to demonstrate their idea that a routine gynecological procedure already in widespread use can be leveraged to dramatically reduce the number of deaths due to ovarian cancer.

The Frazer Lab has a number of active research projects related to finding cures and treatment options for a variety of cancers and cardiovascular disease. The lab director, Kelly Frazer, is a world-renowned leader in the field of Genomics with over three decades of experience in research. As director, she contributes both to the knowledge database of the human genetic sequence, while also working on tool development for more accurate and swifter measurements. The lab’s work with cancer takes advantage of the data generated by large public organizations, such as The Cancer Genome Atlas (TCGA), to study a variety of cancer types including chronic lymphocytic leukemia (CLL), breast cancer, and ovarian cancer. The group uses innovative bioinformatics (computational analysis of biological data), statistical approaches, and wet lab experiments to identify and understand the role of inherited genetic variants and somatic mutations in tumors. With respect to ovarian cancer, the lab is developing a novel approach for detecting tumors at early growth stages, which will greatly improve the prognosis of patients.

When it comes to cancer, the surest way to save lives is to detect a tumor early when it is small and relatively innocuous. Small tumors that have not spread to other parts of the body typically can be swiftly and successfully eradicated from the body. At present there is no test available that women can use to detect the presence of a small ovarian tumor developing within their bodies. The dramatic reduction in suffering and death that could be had through early detection of ovarian cancer has been the strong, motivating reason why many biomarkers—nearly all blood-based—have been proposed in recent years for ovarian cancer detection. In 2011, two large, multi-center studies representing the first systematic and reliable evaluations of these proposed blood-based biomarkers were concluded. These studies soberly reported that none of the evaluated biomarkers were effective. These results clearly indicate the difficulty of developing a test for early detection of ovarian cancer and call for new approaches to the problem. Dr. Barrett has conceptualized a new strategy for the early detection of ovarian cancer that is based on a new understanding of ovarian tumor cell migration, new DNA sequencing technologies and techniques, and novel computer algorithms that he has developed:

• The transcription of DNA into RNA is a fundamental process that occurs in all cells. One of the key characteristics in tumors is the deregulation of transcription and splicing control circuits, which can result in the production of RNA molecules that are not present in normal tissues. Detecting such improperly made RNA molecules in a cell would identify that cell as a tumor cell. In order for such a detection method to work, one must first discover the tumor-specific RNA molecules that result from the deregulated transcription and splicing control circuits. As a result of five years of research, Dr. Barrett has developed a systematic process for discovering tumor-specific RNA molecules. He has applied this process to ovarian cancer and has identified RNA molecules that only exist in ovarian tumors.

• It is now known that ovarian tumor cells can migrate from the primary tumor site in the ovaries down the fallopian tube to the cervix. The cervical tissue that is collected in the routine Pap test is at present only used to test for cervical cancer. Dr. Barrett intends to extend the lifesaving power of the Pap test by detecting the presence of even a few tumor cells in the collected tissue by detecting the presence of ovarian tumor-specific RNA molecules that he has discovered. Because a Pap test is part of a routine gynecologic examination, the success of Dr. Barrett’s approach would mean that any woman who sees a gynecologist could be screened for ovarian cancer.