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Herceptin: increasing survival in metastatic breast cancer
1Division of Hematology-Oncology, UCLA School of Medicine, Room 11-244, Factor Building, 10833 Le Conte Avenue, Los Angeles, California 90095-1678, USA.
Abstract:
Growth factors and their receptors play an important role in the pathogenesis of human cancer. The human epidermal growth factor receptor-2 (HER2) is overexpressed in approximately 30% of breast cancers and this is associated with poor clinical outcome. Overexpression of HER2 has been demonstrated to play a direct role in oncogenic transformation. Murine monoclonal antibodies (muMAbs) targeting the extracellular domain of the HER2 receptors suppress HER2-positive cancer cell growth, with muMAb 4D5 having particularly potent activity. A humanized form of muMAb 4D5 was generated by converting all but the antigen-binding region of muMAb 4D5 into human IgG consensus sequences. The humanized monoclonal antibody, Herceptin, preferentially targets HER2-overexpressing cells, produces responses in breast cancer patients and is well tolerated. In a pivotal phase III trial, Herceptin administered in combination with chemotherapy (anthracycline/cyclophosphamide or paclitaxel) was compared with chemotherapy alone. The combination was found to produce significant survival benefits in HER2-positive metastatic breast cancer patients. These results have led to the approval of Herceptin for clinical use in the USA and elsewhere.
Insights
Humanized monoclonal antibody Herceptin targets HER2-overexpressing breast cancer cells. Combining Herceptin with chemotherapy significantly improves survival in patients with HER2-positive metastatic breast cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Growth factors and their receptors are crucial in human cancer development.
- Human epidermal growth factor receptor-2 (HER2) overexpression in ~30% of breast cancers correlates with poor prognosis.
- HER2 overexpression contributes directly to oncogenic transformation.
Purpose of the Study:
- To evaluate the efficacy and safety of a humanized monoclonal antibody targeting HER2 in breast cancer treatment.
- To compare the combination of Herceptin with chemotherapy against chemotherapy alone in HER2-positive metastatic breast cancer.
Main Methods:
- Development of a humanized monoclonal antibody (Herceptin) from a murine antibody (muMAb 4D5) targeting the HER2 extracellular domain.
- A pivotal phase III clinical trial comparing Herceptin plus chemotherapy versus chemotherapy alone.
- Treatment regimens included anthracycline/cyclophosphamide or paclitaxel as chemotherapy.
Main Results:
- Herceptin preferentially targets HER2-overexpressing cells and is well-tolerated.
- The combination of Herceptin and chemotherapy demonstrated significant survival benefits compared to chemotherapy alone.
- Significant improvements in survival were observed in HER2-positive metastatic breast cancer patients.
Conclusions:
- Herceptin is an effective targeted therapy for HER2-positive breast cancer.
- Combination therapy with Herceptin and chemotherapy offers significant survival advantages for metastatic disease.
- Herceptin has been approved for clinical use based on its demonstrated efficacy and safety.