Proposed Mechanisms of Action

Based on preclinical studies, Herceptin suppresses HER2 activity via two domains

Herceptin works on both the extracellular and the intracellular domains of the HER2 receptor ^2,3-5

Continuously suppresses HER2 activity that may lead to tumor proliferation ³
Leads to cell stasis and death

In preclinical studies, synergy with Herceptin (trastuzumab) enhanced the effects of chemotherapy ^4,6,7
Herceptin provides constant inhibition of the HER2 receptor ¹
- Extended half-life enables Herceptin to maintain constant exposure
Because Herceptin works on both the intracellular and extracellular domains of the HER2 receptor:
- Mechanisms promoting resistance within the cell may not render Herceptin inactive
- Herceptin that is bound to a HER2 receptor may still work extracellularly to signal the immune system to destroy the cell

References:
1. Herceptin® (trastuzumab) Full Prescribing Information, Genentech, Inc. May 2008.
2. Gago EE, Fanelli MA, Ciocca DR. Co-expression of steroid hormone-receptors (estrogen receptor alpha and/or progesterone receptors) and Her2/neu (c-erbB-2) in breast cancer: clinical outcome following tamoxifen-based adjuvant therapy. JSteroid Biochem Mol Biol.2006; 98: 36-40.
3. Yakes FM, Chinratanalab W, Ritter CA, et al. Herceptin-induced inhibition of phosphatidylinositol-3 kinase and AktIs required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res.2002; 62(14):4132-4141.
4. Arnould L, Gelly M, Penault-Llorca F, et al. Trastuzumab-based treatment of HER2+ breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br J Cancer.2006;94(2):259-267.
5. Bianco AR. Targeting c-erbB2 and other receptors of the c-erb B family: rationale and clinical applications. JChemother. 2004; 16 Suppl 4:52-54.
6. Pegram MD, Konecny GE, O'Callaghan C, et al. Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. JNatl Cancer Inst. 2004; 96: 739-749.
7. Baselga J, Norton L, Albanell J, Kim Y-M, Mendelsohn J. Recombinant humanized anti-HER2 antibody (Herceptin^™) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res.1998;58:2825-2831.
8. Lewis GD, FigariI, Fendly B,et al. Differential responses of human tumor cell lines to anti p185HER2 monoclonal antibodies. Cancer Immunol Immunother.1993;37(4):255-263.
9. Yarden Y. Biology of HER2 and its importance in breast cancer. Oncology. 2001;61(suppl2):1 13.
10. Harari D, Yarden Y. Molecular mechanisms underlying ErbB2/HER2 action in breast cancer. Oncogene. 2000;19(53):6102-6114.

Proposed Mechanisms of Action

Based on preclinical studies, Herceptin suppresses HER2 activity via two domains

Herceptin works on both the extracellular and the intracellular domains of the HER2 receptor 2,3-5

Herceptin® (trastuzumab)

Share this page

Email this page

Herceptin works on both the extracellular and the intracellular domains of the HER2 receptor ^2,3-5