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HER dimerization inhibitors: developing pertuzumab as an anticancer agent in women's oncology
Don S Dizon1, Sharmila Makhija
1Warren Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Program in Women's Oncology, 101 Dudley Street, RI 02905, Providence, USA +1 401 453 7520 ; +1 401 453 7529 ; ddizon@wihri.org.
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.
Insights
Pertuzumab shows promise in treating HER-2/neu positive breast cancer. Further research is needed for ovarian cancer, potentially targeting women with low HER3 levels.
Area of Science:
- Oncology
- Pharmacology
- Immunotherapy
Background:
- Pertuzumab is a monoclonal antibody targeting the human epidermal growth factor receptor (HER)-2/neu.
- It inhibits HER-2/neu receptor dimerization, crucial for cell signaling.
Purpose of the Study:
- To review the scientific rationale and clinical trial outcomes of pertuzumab.
- Focus on pertuzumab's efficacy in solid tumors, particularly women's cancers.
Main Methods:
- Review of published clinical trial results.
- Inclusion of data presented at national meetings.
Main Results:
- Pertuzumab demonstrates promising activity with trastuzumab in metastatic breast cancer.
- Ovarian cancer results are limited; HER3 levels may identify patients benefiting from pertuzumab.
Conclusions:
- Pertuzumab shows encouraging benefits in HER-2/neu positive breast cancer.
- Preliminary ovarian cancer data suggests potential in a HER3-low subgroup, requiring further investigation.
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