Emerging Diagnostic Biomarkers in Ovarian Cancer

Worldwide, ovarian cancer (CaO) is the leading cause of death from gynecological cancer and the fourth most common cause of cancer death in women. In 2006, according to the American Cancer Society, 20,180 new cases of CaO will be diagnosed in the United States and 15,310 women will die from the disease. This high death rate results from the difficulty associated with detecting CaO at an early stage and the lack of effective therapies to treat advanced disease. As we discuss, physicians are unanimous in calling for the development of a diagnostic test that can identify CaO before it metastasizes. In this report, we examine the pathophysiology of CaO and describe current methods of screening for the cancer, the use of biomarkers to diagnose CaO, proteomic and genomic technologies that researchers are employing to identify and test biomarkers, emerging biomarkers, and the use of biomarkers to improve clinical trials of CaO treatments and ultimately to tailor treatment to the individual patient.

Business Implications
Serum proteomics may yield new biomarkers for the identification of CaO, enabling blood tests for the detection of the disease. The hope is that combining CaO-associated proteins into a multimarker assay may enable screening and improve the chances of detecting CaO in its early stages. Patients would then have a better chance of being cured or a longer median survival and therefore would receive more cycles of treatment. An increase in drug-treatment rates would boost revenue for drug companies with marketed CaO therapies.
Identifying protein markers in the blood that indicate how CaO responds to therapy is another goal of researchers. Specific markers that will give gynecologic oncologists and their patients a better idea of how their disease is responding to treatment will enable them to change treatment if a patient’s tumor is not responding. It will also facilitate longer treatment durations because patients will be able to switch to more suitable therapies and hopefully enjoy longer survival times.
The quest for biomarkers has led to advances in proteomics and DNA microarray analysis and improved understanding of the biology and genetics of CaO. This knowledge, in turn, has led to the identification of multiple molecular targets that may soon change the standard treatment of CaO. Several molecularly targeted (biologic) agents have already entered clinical trials, including angiogenesis inhibitors and epidermal growth factor inhibitors. Further developments in this field will bear more novel highly targeted therapies. These therapies, along with the identification of corresponding biomarkers, will pave the way for the “intelligent” treatment of CaO by identifying patients whose disease will respond to a specific treatment.
A successful diagnostic or screening test for CaO has significant sales potential. Given the lack of definitive diagnostic tests for CaO and the poor prognosis for patients with metastasized disease, physicians are unanimous in emphasizing the need for earlier diagnosis.
A CaO biomarker would greatly reduce the costs associated with drug development by enabling the selection of a more homogeneous patient population for smaller, more cost-effective clinical trials. A biomarker would also accelerate drug development by facilitating decisions regarding which agents to pursue in the early stages of clinical development.