HER dimerization inhibitors: developing pertuzumab as an anticancer agent in women's oncology

Abstract

Background: Pertuzumab is a novel monoclonal antibody that blocks the dimerization domain of the human epidermal growth factor receptor (HER)-2/neu receptor, disabling its ability to form heterodimers with the other members of its family. Objective: We review the background and scientific rationale, but more specifically cover current clinical trial outcomes of pertuzumab in solid tumors, with an emphasis on the work completed in women's cancers. Methods: Clinical trial results published or presented at national meetings are included in this review. Results: Pertuzumab shows promising activity with trastuzumab in the treatment of metastatic breast cancer. The results in ovarian cancer have been limited thus far but a post hoc analysis of the results of a completed randomized Phase II trial of gemcitabine with or without pertuzumab suggests that low HER3 levels may mark a group of women who may benefit from the addition of pertuzumab to chemotherapy. Conclusions: The efficacy of pertuzumab independent of HER-2/neu overexpression remains under investigation. Still, the benefits seen in HER-2/neu positive breast cancer is encouraging. Work in ovarian cancer remains preliminary but the possibility of using pertuzumab in a targeted population with low HER3 levels warrants further evaluation.

Keywords::

• breast cancer
• EGFR pathway
• HER-2/neu
• HER dimerization inhibitors
• ovarian cancer