Lapatinib: a dual inhibitor of EGFR and HER2 tyrosine kinase activity
Lapatinib: a dual inhibitor of EGFR and HER2 tyrosine kinase activity
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DOI：
10.1517/14712598.7.2.257
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发表时间：
2007-02-01
影响因子：
4.6
通讯作者：
Aglietta, Massimo
中科院分区：
文献类型：
--
作者：
Montemurro, Filippo;Valabrega, Giorgio;Aglietta, Massimo
拉帕替尼（GW 572016）是一种表皮生长因子受体（EGFR）和人EGFR-2 （HER2）酪氨酸激酶活性的口服抑制剂，这两种受体在人类恶性肿瘤中都经常发生改变。作为一种多靶点药物，理论上有能力提供更有效的抗肿瘤活性，并延缓肿瘤耐药的发生。基于有希望的临床前结果，拉帕替尼正在癌症患者中广泛研究。在I期临床试验中，拉帕替尼的副作用是有利的，少数患者出现严重的毒性。II期研究表明，拉帕替尼在her2阳性晚期乳腺癌患者中具有有意义的临床活性。不幸的是，它在表皮生长因子受体主导的癌症，如结直肠癌或头颈部鳞状细胞癌中的活性并不高。目前在乳腺癌患者中正在进行一个广泛的项目，以确定拉帕替尼在这种临床环境中的正确作用。对乳腺癌以及其他实体肿瘤的研究也在收集大量的生物学数据。相关研究有望阐明拉帕替尼疗效的预测因素，并应用于临床实践，以便选择患者进行治疗。
Lapatinib (GW 572016) is an oral inhibitor of the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2), which are both frequently altered in human malignant tumors. Being a multitargeting agent, it has the theoretical ability to provide more efficient antitumor activity and delay the onset of tumor resistance. Based on promising preclinical results, lapatinib is being extensively studied in cancer patients. In Phase I clinical trials, the side effect profile of lapatinib results are favorable, with a few patients experiencing serious toxicity. Phase II studies showed that lapatinib has meaningful clinical activity in the setting of HER2-positive advanced breast cancer patients. Unfortunately, its activity in epidermal growth factor receptor-dominated cancers, such as colorectal cancer or squamous cell carcinoma of the head and neck, is modest. An extensive program is now ongoing in breast cancer patients to establish the correct role of lapatinib in this clinical setting. Studies in breast cancer, as well as in other solid tumors are also collecting a large amount of biological data. Correlative studies will hopefully clarify predictive factors of lapatinib efficacy that can be applied in clinical practice in order to select patients for treatment.