HER-dimerization inhibitors: evaluating pertuzumab in women's cancers.
BACKGROUND
Pertuzumab is a human EGF receptor (HER)-dimerization inhibitor that represent a novel class of agents aimed at blocking HER2 from pairing with other receptors of the HER family. In this review, we discuss the background and scientific rationale, related to pertuzumab as it has undergone development for women's cancers.


METHODS
Pre-clinical and clinical trials, published or presented at national meetings from 1995 to the present, are included in this review.


RESULTS
A Phase II trial in HER2-positive metastatic breast cancer showed promising activity of pertuzumab when it was combined with trastuzumab and a randomized Phase III trial is now underway. Pertuzumab, when evaluated in recurrent ovarian cancer showed limited activity when combined with chemotherapy in platinum-sensitive and platinum-resistant disease. However, a recent subset analysis suggests that HER3 mRNA levels may predict response to pertuzumab in ovarian cancer.


CONCLUSIONS
HER-dimerization inhibitors represent a novel mechanism of inhibition of HER pathways. Pertuzumab may play a role in the management of HER2-positive breast cancer. The potential benefit of pertuzumab in ovarian cancer is unclear, but low HER3 levels may suggest a sub-group of patients that can benefit from pertuzumab.
Kristjansdottir
Katrin
K
Warren Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island - Program in Women's Oncology, 101 Dudley Street, Providence, Rhode Island, USA.
Dizon
Don
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D019281:Dimerization; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C485206:pertuzumab