a Department of Internal Medicine , University of Arizona College of Medicine at South Campus , Tucson , AZ , USA.
b Division of Hematology-Oncology , University of Arizona Cancer Center , Tucson , AZ , USA.
Expert Rev Anticancer Ther. 2018 Dec;18(12):1249-1270. doi: 10.1080/14737140.2018.1527688. Epub 2018 Oct 9.
Protein kinases are involved in various cellular functions. About 2% of the human genome encodes for protein kinases. Dysregulation of protein kinases is implicated in various processes of carcinogenesis. The advent of protein kinase inhibitors in cancer therapy has led to a paradigm shift in cancer therapy. Several protein kinase inhibitors have been approved by FDA in the last few decades. Areas covered: This article provides a review of the FDA approved protein kinase inhibitors as of December 2017 for the well-known oncogenic protein kinases. A list of FDA approved protein kinase inhibitors and their FDA approved clinical indications were cataloged. The role of the respective oncogenic protein kinases in carcinogenesis and cancer progression and the relevant landmark clinical trials of respective protein kinase inhibitors leading up to the FDA approval were PubMed searched and discussed. Expert commentary: Further understanding of the molecular origin of various cancers would help identify new targets. Use of biomarker profiling might select the patient population that would benefit better from kinase inhibitors. Clinical trials should be designed to identify the appropriate sequence of the available kinase inhibitors. It would prove to be useful to test these drugs in the adjuvant setting.
蛋白激酶参与各种细胞功能。人类基因组约有 2%的编码蛋白激酶。蛋白激酶的失调与致癌作用的多个过程有关。蛋白激酶抑制剂在癌症治疗中的出现导致癌症治疗发生了范式转变。在过去几十年中，FDA 已经批准了几种蛋白激酶抑制剂。涵盖领域：本文回顾了截至 2017 年 12 月 FDA 批准的用于著名致癌蛋白激酶的蛋白激酶抑制剂。列出了 FDA 批准的蛋白激酶抑制剂及其 FDA 批准的临床适应证，并对各自的致癌蛋白激酶在致癌作用和癌症进展中的作用以及相应的蛋白激酶抑制剂的相关标志性临床试验进行了搜索和讨论，这些临床试验促成了 FDA 的批准。专家评论：进一步了解各种癌症的分子起源将有助于确定新的靶点。使用生物标志物分析可能会选择更能从激酶抑制剂中获益的患者群体。应设计临床试验以确定可用激酶抑制剂的适当顺序。在辅助治疗中测试这些药物将被证明是有用的。
