Kirschbaum M H, Yarden Y
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
J Cell Biochem Suppl. 2000;34:52-60.
Cancer chemoprevention trials can be directed at targeting established molecular mechanisms which contribute to neoplasia. One potential target is the ErbB/HER family of growth factor receptors with intrinsic tyrosine kinase activity. This group of four receptors mediates the action of multiple stromal ligands of the EGF/neuregulin family on the adjacent epithelium. Aberrant autocrine loops and overexpression of certain receptors, especially ErbB-2 (also called HER2 or Neu), play a role in fixation and propagation of oncogenic mutations. Here we concentrate on ErbB-2 and epithelial cancer and discuss current and future therapeutic strategies that may limit cancer, particularly in patients who are at high risk after removal of the primary tumor. Because ErbB-2 acts as a shared co-receptor, and its heterodimers are relatively potent receptor combinations, it offers selectivity that spares other routes of signal transduction. Immunotherapy, as well as gene therapy and tyrosine kinase inhibitors specific to ErbB-2 may join the ranks of effective chemopreventive agents.
癌症化学预防试验可针对那些导致肿瘤形成的既定分子机制。一个潜在的靶点是具有内在酪氨酸激酶活性的表皮生长因子受体（ErbB/HER）家族。这一组四个受体介导了表皮生长因子/神经调节蛋白（EGF/neuregulin）家族的多种基质配体对相邻上皮细胞的作用。异常的自分泌环以及某些受体（特别是ErbB-2，也称为HER2或Neu）的过表达，在致癌突变的固定和传播中发挥作用。在这里，我们聚焦于ErbB-2与上皮癌，并讨论当前及未来可能限制癌症发生的治疗策略，尤其是对于那些在切除原发性肿瘤后处于高风险的患者。由于ErbB-2作为一种共享的共受体，并且其异二聚体是相对强效的受体组合，它提供了对其他信号转导途径的选择性保护。免疫疗法以及针对ErbB-2的基因疗法和酪氨酸激酶抑制剂可能会成为有效的化学预防药物。
