Targeting HER2 in other tumor types

The human epidermal growth factor receptor-2 (HER2) is overexpressed/amplif ied in a range of tumor types including breast, ovarian, bladder, salivary gland, endometrial, pancreatic and non-small-cell lung cancer (NSCLC). HER2 is implicated in disease initiation and progression, associated with poor prognosis, and may also predict the response to chemotherapy and hormonal t herapy. Anti-HER2 monoclonal antibodies (MAbs) have been designed to specif ically antagonize the function of the HER2 receptor in HER2-positive tumors . Clinical phase II and III trials have demonstrated the efficacy of the hu manized anti-HER2 MAb, trastuzumab (Herceptin), both as a single agent and in combination with chemotherapy in HER2-positive, metastatic breast cancer patients. However, the prevalence of HER2 overexpression/amplification in various tumor types raises the possibility of using anti-HER2 MAbs to antag onize the abnormal function of overexpressed HER2 receptors in HER2-positiv e tumors other than breast. Preliminary in vitrostudies indicate that anti- HER2 MAbs suppress the proliferation of ovarian, gastric and NSCLC cell lin es that overexpress the HER2 receptor. These results indicate that anti-HER 2 MAbs may have important therapeutic significance in patients presenting w ith these or other human carcinomas. Clinical trials are either planned or underway to assess the therapeutic role of trastuzumab in NSCLC, bladder an d ovarian cancer.