The effect of HER-2/neuoverexpression 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/neuamplification 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 HER-2/neu overexpression to be associated with estrogen receptor negativity, poor tumor celldifferentiation, 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.
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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]
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]
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]