HER-2/Neu and Chemotherapy
The effect of HER-2/neu overexpression on the effectiveness of chemotherapy drugs has not been fully elucidated. Several studies have been conducted to ascertain the effects of the HER2 protein on responses to chemotherapy. One recent study exposed the cells of 140 primary breast tumors to various concentrations of two different chemotherapy combinations. The study showed that cells with strong HER-2/neu overexpression exhibited greater growth inhibition with the chemotherapy treatments than those with lower expression levels. The HER-2/neu amplification seemed to impart chemotherapy sensitivity to the tumor cells rather than making them more drug resistant. Chemotherapy attacks cells that are replicating, and HER-2/neu amplification causes faster replication. One possible conclusion would be that due to their high rate of cell division, the HER2 overexpressing cancer cells are killed off more effectively. The actual effects of HER-2/neu amplification is still in question because there have been some contradictory results showing a lack of effect on chemotherapy.1
Other work has shown that HER-2/neu overexpression to be associated with estrogen receptor negativity, poor tumor cell differentiation, and decreased patient survival.2 It is clear that this proto-oncogene is important in the development of several forms of cancer but the story is far from complete.
Antibody treatment and HER2
Cancer treatments have been designed to combat cancers overexpressing the HER2 protein. Trastuzumab (Herceptin®), from Genentech, is a humanized monoclonal antibody that binds to the HER2 protein and blocks its activity, preventing excessive cell proliferation. This process is shown in the animation below. Herceptin® has been used recently in conjunction with chemotherapy for HER-2/neu amplified cancers.23 More on antibody treatments for cancer.
- 1. Konecny G, Fritz M, Untch M, Lebeau A, Felber M, Lude S, Beryt M, Hepp H, Slamon D, Pegram M. "Her-2/neu Overexpression and in vitro Chemosensitivity to CMF and FEC in Primary Breast Cancer." Breast Cancer Research and Treatment (2001). 69: 53-63. [PUBMED]
- 2. a. b. Spizzo G, Obrist P, Ensinger C, Theurl I, Dunser M, Ramoni A, Gunsilius E, Eibl G, Mikuz G, Gastl G. "Prognostic Significance of Ep-CAM and Her-2/neu Overexpression in Invasive Breast Cancer." Int. J. Cancer (2002). 98: 883-888. [PUBMED]
- 3. Tsuda H, Akiyama F, Terasaki H, Hasegawa T, Kurosumi M, Shimadzu M, Yamamori S, Sakamoto G. "Detection of Her-2/neu (c-erb B-2) DNA Amplification in Primary Breast Carcinoma." Cancer (2001). 92(12): 2965-2974. [PUBMED]