Effects of HER-2/neu on chemosensitivity of tumor cells.

In solid tumors, such as breast and ovarian cancer, the predominant genetic mechanism for oncogene activation is through gene amplification. The HER-2 (also known as ErbB2/c-erbB2/HER-2 / neu) oncogene is the most frequently amplified oncogene in breast cancer and its overexpression is associated with poor clinical outcome. In addition to its role in tumor progression, HER-2 has been implicated in altering tumor cell chemosensitivity to cytotoxic chemotherapy, particularly to anthracyclines. However, sophisticated in vitro studies have recently indicated that HER-2 may not have anything to do with the sensitivity of the cancer cells to cytotoxic drugs. Topoisomerase IIalpha gene is a target gene for many cytotoxic drugs and is located just by the HER-2 at the 17q12-q21. TopoIIalpha amplification and deletion may account for both relative chemosensitivity and resistance to anthracycline-therapy depending on the specific genetic defect at the topoIIalpha locus. Whereas HER-2 is an oncogene that clearly can drive tumor induction and growth, its function as a marker for chemoselection may be due to associated genetic changes in the topoIIalpha gene. Copyright 2000 Harcourt Publishers Ltd.