摘要
分子靶标药物的发展,从用于治疗慢性粒细胞白血病的伊马替尼或者治疗非小细胞肺癌的吉非替尼开始,得到了飞速发展。表皮生长因子受体络氨酸激酶抑制剂(EGFR-TKIs)已经发展到第二和第三代,以抵抗EGFR-TKI为作用机制的蛋氨酸激活剂的新药研发也正在进行。虽然新的抗癌药物时代正朝着分子靶标药物时代发展,用于药物研发的方法与以前相比并无区别。另外,药动学(PK)和药效学(PD)对于药物开发非常重要,也有新的证据证明药物基因组学也非常重要,因为某些类型的基因改变可能极大地影响药物代谢、排泄,尤其是临床疗效。考虑到这些因素可能会影响到PK/PD,所以确定抗癌药物的最佳剂量是必须的。下面的文章对用于治疗非小细胞肺癌的EGFR/Met抑制剂的临床发展和这些药物的临床药理学进行了综述。
关键词: 表皮生长因子受体,蛋氨酸,非小细胞肺癌,药理学
Current Drug Targets
Title:Clinical Pharmacology of EGFR/Met Inhibitors in Non-Small Cell Lung Cancer
Volume: 15 Issue: 14
Author(s): Shigehiro Yagishita and Akinobu Hamada
Affiliation:
关键词: 表皮生长因子受体,蛋氨酸,非小细胞肺癌,药理学
摘要: Development of molecular targeting agents, starting with imatinib for chronic myeloid leukemia or gefitinib for non-small cell lung cancer (NSCLC), has recently progressed at a rapid rate. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have already been developed to the 2nd and 3rd generation, and novel drug development targeted towards Met activation, which is an EGFR-TKI resistance mechanism, is ongoing. Although the era of new anticancer agents is moving towards an era of molecular targeting agents, the methods used for drug development are not different than before. In addition to the importance of pharmacokinetics (PK) and pharmacodynamics (PD) for drug development, emerging evidence is also demonstrating the significance of pharmacogenomics, since certain types of gene alteration may greatly affect drug metabolism, excretion, and notably, clinical efficacy. It is desirable to determine optimal doses of anticancer drugs by taking into account these factors that could potentially influence PK/PD. The following article reviews the clinical development of EGFR/Met inhibitors for NSCLC and the clinical pharmacology of these drugs.
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Yagishita Shigehiro and Hamada Akinobu, Clinical Pharmacology of EGFR/Met Inhibitors in Non-Small Cell Lung Cancer, Current Drug Targets 2014; 15 (14) . https://dx.doi.org/10.2174/1389450115666141110154838
DOI https://dx.doi.org/10.2174/1389450115666141110154838 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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