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The ErbB receptors as targets for breast cancer therapy
1Medical Oncology Service, Hospital Universitari Vall d' Hebron, Barcelona, Spain.
Abstract:
Breast carcinomas express high levels of ErbB receptors and their ligands, and their overexpression has been associated with a more aggressive clinical behavior. For these reasons therapies directed at these receptors have the potential to be useful anti-cancer treatments. A series of monoclonal antibodies (MAbs)3 directed against the EGF (ErbB1) receptor and the closely related HER2/Neu (ErbB2) receptor are currently under evaluation. These MAbs have shown promising preclinical activity and "chimeric" and "humanized" MAbs have been produced in order to obviate the problem of host immune reactions. These antibodies are currently being tested in clinical trials either alone or in combination with chemotherapeutic agents. Clinical activity with one of these antibodies, trastuzumab, a humanized anti-ErbB2 MAb, has been documented in patients with breast cancer in a series of clinical trials and has recently been approved for the therapy of patients with metastatic ErbB2 overexpressing breast cancer. In addition to antibodies, compounds that inhibit receptor tyrosine kinases have shown significant preclinical activity and are currently being evaluated in the clinic.
Insights
Targeting ErbB receptors with monoclonal antibodies (MAbs) shows promise for breast cancer treatment. Trastuzumab, an anti-ErbB2 MAb, is approved for metastatic ErbB2-overexpressing breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Breast carcinomas frequently overexpress ErbB receptors and their ligands, correlating with aggressive clinical behavior.
- Targeting these receptors offers a potential therapeutic strategy for anti-cancer treatments.
Purpose of the Study:
- To evaluate the efficacy of monoclonal antibodies (MAbs) targeting Epidermal Growth Factor Receptor (EGFR, ErbB1) and Human Epidermal growth factor Receptor 2 (HER2/Neu, ErbB2) in breast cancer.
- To assess the clinical activity of trastuzumab, a humanized anti-ErbB2 MAb, in patients with metastatic ErbB2-overexpressing breast cancer.
Main Methods:
- Development and evaluation of monoclonal antibodies (MAbs) against ErbB1 and ErbB2 receptors.
- Preclinical studies demonstrating MAb activity, including the production of chimeric and humanized MAbs to minimize host immune reactions.
- Clinical trials testing MAbs alone or in combination with chemotherapy.
Main Results:
- Promising preclinical activity observed with MAbs targeting ErbB1 and ErbB2.
- Trastuzumab (a humanized anti-ErbB2 MAb) has demonstrated documented clinical activity in breast cancer patients.
- Trastuzumab is now approved for treating metastatic ErbB2-overexpressing breast cancer.
Conclusions:
- Therapies targeting ErbB receptors, particularly monoclonal antibodies like trastuzumab, are effective against breast cancer.
- Further evaluation of receptor tyrosine kinase inhibitors is ongoing for potential anti-cancer applications.