Calce Enrica, Monfregola Luca, Saviano Michele, De Luca Stefania
Institute of Biostructures and Bioimaging, National Research Council, 80138 Naples, Italy.
Curr Med Chem. 2015;22(21):2525-38. doi: 10.2174/0929867322666150521091103.
HER2 receptor, for its involvement in tumorigenesis, has been largely studied as topic in cancer research. In particular, the employment of trastuzumab (Herceptin), a humanized anti-HER2 antibody, showed several clinical benefits in the therapy against the breast cancer. Moreover, for its accessible extracellular domain, this receptor is considered an ideal target to deliver anticancer drugs for the receptormediated anticancer therapy. By now, monoclonal antibody and its fragments, affibody, and some peptides have been employed as targeting agents in order to deliver various drugs to HER2 positive tumor cells. In particular, the ability to perform a fast and reliable screening of a large number of peptide molecules would make possible the selection of highly specific compounds to the receptor target. In this regard, the availability of preparing a simplified synthetic model which is a good mimetic of the receptor target and can be used in a reliable screening method of ligands would be of a strategic importance for the development of selective HER2-targeting peptide molecules. Herein, we illustrate the importance of HER2-targeted anticancer therapies. We also report on a synthetic and effective mimetic of the receptor, which revealed to be a useful tool for the selection of specific HER2 ligands.
由于HER2受体参与肿瘤发生，它在癌症研究中一直是一个被广泛研究的课题。特别是，人源化抗HER2抗体曲妥珠单抗（赫赛汀）的应用在乳腺癌治疗中显示出多种临床益处。此外，由于其可及的细胞外结构域，该受体被认为是用于受体介导的抗癌治疗中递送抗癌药物的理想靶点。到目前为止，单克隆抗体及其片段、亲和体和一些肽已被用作靶向剂，以便将各种药物递送至HER2阳性肿瘤细胞。特别是，能够对大量肽分子进行快速可靠的筛选将使得有可能选择对受体靶点具有高度特异性的化合物。在这方面，制备一种简化的合成模型，该模型是受体靶点的良好模拟物，并且可用于可靠的配体筛选方法，这对于开发选择性HER2靶向肽分子具有战略重要性。在此，我们阐述了HER2靶向抗癌治疗的重要性。我们还报告了一种受体的合成有效模拟物，它被证明是选择特异性HER2配体的有用工具。
