The University of Tokyo, Graduate School of Medicine, Department of Gastroenterology, Japan.
Expert Opin Investig Drugs. 2011 May;20(5):595-604. doi: 10.1517/13543784.2011.566863. Epub 2011 Mar 16.
Inhibitors targeting oncogenic kinases, especially receptor tyrosine kinases (RTKs), are being vigorously developed, and some have been demonstrated to be effective in clinical settings. The amplification of certain RTKs (ErbB2, c-Met and FGFR2) is associated with gastric cancer progression, but the only recently approved inhibitor is trastuzumab, ErbB2-targeting antibody. Other well-known oncogenic kinases (PI3K and RAF) are also activated in a small portion of gastric cancers. Drugs targeting these kinases are promising and should be approved in an appropriate and expeditious way.
This article reviews novel inhibitors emerging in the field of advanced gastric cancer, based on basic research concerning altered oncogenes and the clinical trials of drugs targeting these oncogenes.
Promising inhibitors of gastric cancer may be found in not only new investigative agents but also agents currently being used against other malignancies. The appropriate design for clinical trials of molecularly targeted therapeutic agents is also important. Targeted therapies tailored to individual genomic profiles would provide a more personalized treatment for advanced gastric cancer.
针对致癌激酶，尤其是受体酪氨酸激酶（RTKs）的抑制剂正在被大力开发，一些抑制剂已被证明在临床环境中有效。某些 RTKs（ErbB2、c-Met 和 FGFR2）的扩增与胃癌的进展有关，但唯一最近获得批准的抑制剂是针对 ErbB2 的抗体曲妥珠单抗。其他知名的致癌激酶（PI3K 和 RAF）也在一小部分胃癌中被激活。针对这些激酶的药物很有前景，应该以适当和迅速的方式获得批准。
本文基于有关改变的癌基因的基础研究和针对这些癌基因的药物的临床试验，综述了晚期胃癌领域新兴的新型抑制剂。
不仅可以从新的研究药物中找到有前途的胃癌抑制剂，也可以从目前用于治疗其他恶性肿瘤的药物中找到。针对分子靶向治疗药物的临床试验的适当设计也很重要。针对个体基因组图谱定制的靶向治疗将为晚期胃癌提供更个性化的治疗。
