Creedon Helen, Brunton Valerie G
Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Crit Rev Oncog. 2012;17(2):145-59. doi: 10.1615/critrevoncog.v17.i2.20.
Src is the cellular counterpart of the first identified viral oncogene v-Src. It forms part of a large family of nonreceptor tyrosine kinases that have been extensively studied over the last few decades. This has led to the realization that Src can regulate a number of signaling pathways that impact on the behavior of tumor cells, including proliferation, survival, migration, invasion, and angiogenesis. There are currently four Src inhibitors (dasatinib, saracatinib, bosutinib, and KX01) in clinical development, and although there is a plethora of information on their activity in preclinical models their clinical efficacy has been disappointing. Here we review the current status of the Src inhibitors and highlight the difficulties involved in assessing these therapeutics in the clinical setting. In the future it will be important to combine our knowledge of basic Src biology with the use of appropriate preclinical models to aid the design of clinical trials. Taking this integrated approach will hopefully help to realize the true potential of Src kinase inhibitors.
Src是首个被鉴定出的病毒癌基因v-Src在细胞中的对应物。它是一大类非受体酪氨酸激酶家族的成员，在过去几十年里得到了广泛研究。这使得人们认识到，Src可调节许多影响肿瘤细胞行为的信号通路，包括增殖、存活、迁移、侵袭和血管生成。目前有四种Src抑制剂（达沙替尼、萨拉替尼、博舒替尼和KX01）正处于临床开发阶段，但尽管在临床前模型中有大量关于它们活性的信息，其临床疗效却令人失望。在此，我们综述Src抑制剂的当前状况，并强调在临床环境中评估这些治疗药物所涉及的困难。未来，将我们对Src基础生物学的认识与使用合适的临床前模型相结合，对于辅助设计临床试验至关重要。采用这种综合方法有望帮助实现Src激酶抑制剂的真正潜力。
