HER1/EGFR targeting:: Refining the strategy
HER1/EGFR targeting:: Refining the strategy
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DOI：
10.1634/theoncologist.9-1-58
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发表时间：
2004-01-01
期刊：
影响因子：
5.8
通讯作者：
Pérez-Soler, R
中科院分区：
文献类型：
--
作者：
Pérez-Soler, R
人表皮生长因子受体(HER)靶向已经形成了不同公司广泛且不断增长的药物开发计划的基础。然而，受体生物学往往解释不力，令人困惑。HER家族的四个天然受体和一个肿瘤特异性突变体可以通过一系列复杂和复杂的机制激活信号，这一点我们才刚刚开始了解。HER1/EGFR下游信号可通过一系列过程导致肿瘤的生长和发展，包括促进细胞增殖、存活和转移。HER信号系统中存在一系列潜在的治疗靶点，包括细胞内外。单抗和酪氨酸激酶抑制剂分别作用于细胞外和细胞内，包括两类最先进的临床开发药物或已可使用的药物。尽管在化疗耐药的非小细胞肺癌(NSCLC)患者中前景看好，但酪氨酸激酶抑制剂吉非替尼在非小细胞肺癌(NSCLC)的两个III期试验令人失望的结果让一些人感到担忧。然而，许多因素可能导致了这一结果，这并不一定预示着这些药物未来的有用性。患者特征、缺乏患者选择、给药计划和试验设计可能都起到了作用。重要的是要记住，细胞内靶向HER是一种相对新颖的方法，我们关于如何最好地优化这种治疗的知识仍在展开。需要更多的临床经验。
Human epidermal growth factor receptor (EGFR), HER, targeting has formed the basis of extensive and growing drug development programs in various companies. However, receptor biology is often poorly explained and confusing. The HER family of four naturally occurring receptors and one tumor-specific mutant can activate signaling via a complex and sophisticated range of mechanisms, which we are only beginning to understand. HER1/EGFR downstream signaling can lead to tumor growth and development via a host of processes, including enhanced cellular proliferation, survival, and metastasis. A range of potential therapeutic targets exists within the HER signaling system, both inside and outside the cell. Monoclonal antibodies and tyrosine kinase inhibitors, acting extracellularly and intracellularly, respectively, comprise two classes of agents most advanced in clinical development or already available for use. Despite promising single-agent activity in chemotherapy-resistant patients with non-small cell lung cancer (NSCLC), disappointing results from two phase III trials of the tyrosine kinase inhibitor gefitinib in NSCLC have been of concern to some. However, many factors may have contributed to this outcome, and it is not necessarily predictive of the future usefulness of these agents. Patient characteristics, lack of patient selection, dosing schedule, and trial design may all have played roles. It is important to remember that intracellular targeting of HER is a relatively novel approach, and our knowledge of how best to optimize such treatment is still unfolding. More clinical experience is needed.