Arteaga Carlos
Division of Oncology, Vanderbilt University School of Medicine, 2220 Pierce Avenue, 777 PRB, Nashville, TN 37232-6307, USA.
Semin Oncol. 2003 Jun;30(3 Suppl 7):3-14.
The varying efficacy and toxicity of traditional cancer therapies has driven the development of novel target-based agents. Members of the HER (Human Epidermal Receptor) family, in particular epidermal growth factor receptor (HER1/EGFR), are attractive therapeutic targets because they are overexpressed and/or dysregulated in many solid tumors. Activation of HER1/EGFR mediated through ligand binding triggers a network of signaling processes that promote tumor cell proliferation, migration, adhesion, and angiogenesis, and decrease apoptosis. Therefore, inhibiting HER1/EGFR activity could effectively block downstream signaling events and, consequently, tumorigenesis. Various approaches are being investigated to target members of the HER family, particularly HER1/EGFR and HER2. At the forefront are monoclonal antibodies and small molecules that inhibit the receptor tyrosine kinase activity. Monoclonal antibodies have been developed that act against HER1/EGFR and HER2. Monoclonal antibodies block ligand binding and prevent ligand-induced activation. Tyrosine kinase inhibitors block receptor phosphorylation, preventing downstream signal transduction. Several HER1/EGFR-targeted agents are advanced in clinical development and attention is focused on optimizing their clinical use. While this process may prove challenging, it promises to be beneficial.
传统癌症疗法的疗效和毒性各异，推动了新型靶向药物的研发。HER（人表皮受体）家族成员，尤其是表皮生长因子受体（HER1/EGFR），是颇具吸引力的治疗靶点，因为它们在许多实体瘤中过度表达和/或失调。通过配体结合介导的HER1/EGFR激活会触发一系列信号传导过程，促进肿瘤细胞增殖、迁移、黏附和血管生成，并减少细胞凋亡。因此，抑制HER1/EGFR活性可有效阻断下游信号事件，进而抑制肿瘤发生。目前正在研究多种靶向HER家族成员的方法，尤其是HER1/EGFR和HER2。最前沿的是抑制受体酪氨酸激酶活性的单克隆抗体和小分子。已开发出针对HER1/EGFR和HER2的单克隆抗体。单克隆抗体可阻断配体结合并防止配体诱导的激活。酪氨酸激酶抑制剂可阻断受体磷酸化，防止下游信号转导。几种靶向HER1/EGFR的药物正处于临床开发的 advanced 阶段，人们关注的焦点是优化它们的临床应用。虽然这一过程可能具有挑战性，但有望带来益处。 （注：原文中“advanced”一词在这里的准确意思不太明确，翻译时保留了英文，可能影响整体译文的流畅性，你可根据实际情况进一步调整。）
