Artigo de revisão bibliográfica Mestrado Integrado em Medicina Targeted therapy in ovarian cancer: novel agents and predictive biomarkers

Ovarian cancer is the second most common gynecological malignancy and the leading cause of death from gynecological cancer. Most women present with advanced stage disease, having a poor prognosis even with adequate treatment. Cure is unlikely for advanced disease. Despite the high rate of initial response to chemotherapy, the majority of women will develop recurrent disease, and, thus, new therapeutic options are required. Molecularly directed therapy has been developing rapidly for ovarian cancer, either as single therapy or in association with chemotherapy. Bevacizumab, an anti-VEGF antibody, is among the most promising agents as in phase III clinical trials it appeared to improve survival. PARP inhibitors may also have an important role for patients with BRCA1/BRCA2 mutations. This article will review the various targeted approaches under investigation in ovarian cancer, its current developments, clinical benefits, safety and also searching for predictive biomarkers of response to treatment. Introduction Ovarian cancer is the second most common gynecological malignancy and is by far the most lethal gynecological cancer. For the year 2010, it is estimated that 21,880 new cases will be diagnosed and that 13,850 patients will die from ovarian cancer [1]. The overall prognosis of this malignancy is poor, with a fiveyear overall survival of 45% for all stages [1]. Most ovarian cancers are of epithelial origin and its staging is performed according to the FIGO staging system, which differentiates early stage tumors (stage I-II) from advanced disease (III-IV). The later corresponds to 75% of patients and carries a poor prognosis. Most women present with advanced disease due to the unspecificity of symptoms and the often asymptomatic course in the early stages of this malignancy. The current therapeutic approach consists on the combination of maximal cytoreductive surgery followed by firstline chemotherapy based on platinum compounds (carboplatin or cisplatin) plus paclitaxel. Intraperitoneal drug administration and neoadjuvant chemotherapy are clinically acceptable variations of treatment regimens as they may benefit some patients, but it should be selected on an individualized basis. Managing recurrent ovarian cancer There are different criteria for defining relapse in ovarian cancer. These include