Angiogenesis in ovarian cancer: molecular pathology and therapeutic strategies

Ovarian cancer claims the lives of more women in North America each year than all other gynecologic malignancies combined. Despite the high initial response rates of patients with advanced ovarian cancer to aggressive primary surgical debulking followed by combination chemotherapy, the majority of patients will ultimately develop disease recurrence. The high risk of relapse and nearly guaranteed incurability after relapse is due to genetic instability and a high mutation rate of neoplastic cells that together allow for a high risk of selection for drug resistance. Given the seemingly insurmountable obstacle that acquired drug resistance presents in a setting of minimal, often undetectable, residual tumor burden in women with ovarian cancer, antiangiogenic-targeted therapies offer an attractive strategy for enhanced long-term disease-free survival. The past decade has witnessed a substantial proliferation in our knowledge regarding tumor angiogenesis, which has spurred interest in antiangiogenesis drug development. Current clinical trials are evaluating these agents in a variety of solid tumors, including ovarian cancer. Preliminary work has provided hope that the addition of antiangiogenic therapies may be incorporated into the treatment of women afflicted with ovarian cancer and may translate into enhanced survival.