Zhang H T, Wang Q, Greene M I, Murali R
Department of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
Drug News Perspect. 2000 Aug;13(6):325-9.
HER2/neu and the epidermal growth factor receptor (EGFR) are significantly overexpressed in several cancer cells. Overexpression of these two receptors accounts for progression of many types of cancer: breast, ovarian, skin, pancreas and brain. In recent years, several approaches to disable the receptor complexes have shown promise. Antibody-based therapy, kinase inhibitors and other inhibitors of signaling molecules are the major approaches. Our group developed the concept that an anti-p185HER2/neu monoclonal antibody might represent a therapeutic for cancer and this has culminated in a clinically useful therapeutic, the humanized monoclonal antibody Herceptin (trastuzumab). We have now developed a small-molecule form of an anti-HER2/neu peptidomimetic (AHNP) that exhibit functions comparable to those of the monoclonal antibody Herceptin. This approach may be considered a new paradigm in receptor-specific tumor therapeutics. A brief review of our approach in developing receptor-specific therapeutic agents for HER2/neu-related cancer is presented.
HER2/neu和表皮生长因子受体（EGFR）在多种癌细胞中显著过表达。这两种受体的过表达导致了多种类型癌症的进展，包括乳腺癌、卵巢癌、皮肤癌、胰腺癌和脑癌。近年来，几种使受体复合物失活的方法已显示出前景。基于抗体的疗法、激酶抑制剂和其他信号分子抑制剂是主要方法。我们小组提出了一种概念，即抗p185HER2/neu单克隆抗体可能是一种癌症治疗药物，这最终促成了一种临床有用的治疗药物——人源化单克隆抗体赫赛汀（曲妥珠单抗）。我们现在已经开发出一种抗HER2/neu拟肽（AHNP）的小分子形式，其功能与单克隆抗体赫赛汀相当。这种方法可被视为受体特异性肿瘤治疗的一种新范例。本文简要回顾了我们开发针对HER2/neu相关癌症的受体特异性治疗药物的方法。
