Profile of erlotinib and its potential in the treatment of advanced ovarian carcinoma

The epidermal growth-factor receptor (EGFR) is overexpressed in the majority of epithelial ovarian cancers and promotes cell proliferation, migration and invasion, and angiogenesis, as well as resistance to apoptosis. This makes EGFR an attractive therapeutic target in this disease. A number of strategies to block EGFR activity have been developed, including small-molecular-weight tyrosine kinase inhibitors such as erlotinib. Erlotinib has been evaluated as a single agent in recurrent ovarian cancer, as well as in combination with chemotherapeutic agents in the first-line and recurrent settings, and in combination with the antiangiogenic agent bevacizumab in the recurrent setting, as well as in the maintenance setting after completion of first-line chemotherapy. Unfortunately, erlotinib has shown only minimal efficacy as a single agent, and it has not enhanced the effects of chemotherapy or bevacizumab when combined with these agents. Ongoing and future studies of erlotinib and other agents blocking EGFR will need to define mechanisms resulting in resistance to such interventions, and to validate biomarkers of response to identify patients most likely to benefit from such approaches.