Anticancer drugs: To the rescue?
Anticancer drugs: To the rescue?
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DOI：
10.1038/nrd1428
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发表时间：
2004-06
影响因子：
120.1
通讯作者：
Daniel Jones
中科院分区：
文献类型：
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作者：
Daniel Jones
大多数非小细胞肺癌患者对酪氨酸激酶抑制剂吉非替尼（易瑞沙;阿斯利康）没有反应，尽管那些有反应的患者往往有显着的临床反应。最近的两项研究已经确定了表皮生长因子受体（EGFR）中类似的点突变或缺失突变，这可以预测哪些患者将从吉非替尼中获益。九名吉非替尼反应性肺癌患者中有八名的肿瘤活检携带这些突变，而七名无反应者则没有。佩兹等人在日本的58例乳腺癌中发现了15例EGFR突变，在美国的61例乳腺癌中发现了1例EGFR突变。所选的5份具有EGFR突变的样本中有5份来自治疗应答者。这些突变存在于EGFR酪氨酸激酶结构域的ATP结合口袋中，并与吉非替尼抑制敏感性增加相关。
Most patients with non-small cell lung cancer do not respond to the tyrosine kinase inhibitor gefitinib (Iressa; AstraZeneca), although those who do often have a dramatic clinical response. Two recent studies have identified similar point or deletion mutations in the epidermal growth factor receptor (EGFR) that could be predictive of which patients will benefit from gefitinib. Tumour biopsies from eight out of nine patients with gefitinib-responsive lung cancer carried these mutations, compared with none from seven nonresponders. Paez et al. found EGFR mutations in 15 of 58 unselected tumours from Japan and 1 of 61 from the United States. Five out of five samples selected that had EGFR mutations were from treatment responders. The mutations are found in the ATP-binding pocket of the tyrosine kinase domain of EGFR and are associated with increased sensitivity to inhibition by gefitinib.