Kopetz Scott
Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX.
Gastrointest Cancer Res. 2007;1(4 Suppl 2):S37-41.
Src is a non-receptor protein tyrosine kinase that affects proliferation, angiogenesis, differentiation, migration, invasion, and regulation of apoptosis in colorectal cancer cells. Src activation is a frequent early epigenetic event in colorectal cancer, and is progressively increased in metastatic tumors as compared with primary tumors. Src has also been implicated as a component of epidermal growth factor receptor (EGFR) signal transduction. In particular, Src, as a mediator of receptor transactivation, can uniquely activate EGFR in the absence of EGFR ligand, and a Src inhibitor is synergistic with an EGFR monoclonal antibody in vitro in eliciting growth inhibition. Src inhibition is also synergistic in vivo with platinum chemotherapeutics, further increasing the potential of combination regimens with Src inhibitors. The current Src inhibitors in clinical trials are reviewed.
Src是一种非受体蛋白酪氨酸激酶，它影响结肠直肠癌细胞的增殖、血管生成、分化、迁移、侵袭以及凋亡调控。Src激活是结肠直肠癌中常见的早期表观遗传事件，与原发性肿瘤相比，转移性肿瘤中Src激活呈逐渐增加趋势。Src也被认为是表皮生长因子受体（EGFR）信号转导的一个组成部分。特别是，Src作为受体反式激活的介质，在没有EGFR配体的情况下能够独特地激活EGFR，并且一种Src抑制剂在体外与EGFR单克隆抗体协同作用可引发生长抑制。Src抑制在体内与铂类化疗药物也具有协同作用，进一步增加了与Src抑制剂联合用药方案的潜力。本文对目前正在进行临床试验的Src抑制剂进行了综述。
