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 ErbB(2)/c-erbB2/HER-2/neu) oncogene is the most frequently amplified oncogene in breast cancer and its overexpression is associated wi th 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 vi tro studies have recently indicated that HER-2 may not have anything to do with the sensitivity of the cancer cells to cytotoxic drugs. Topoisomerase II alpha gene is a target gene for many cytotoxic drugs and is located just by the HER-2 at the 17q 12-q21. TopoII alpha amplification and deletion ma y account for both relative chemosensitivity and resistance to anthracyclin e-therapy depending on the specific genetic defect at the topoII alpha locu s. Whereas HER-2 is an oncogene that dearly can drive tumor induction and g rowth, its function as a marker for chemoselection may be due to associated genetic changes in the topoII alpha gene. (C) 2000 Harcourt Publishers Ltd .