Zhang Ming, Jiang Da
Department of Medical Oncology, The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei 050011, P. R. China.
Ai Zheng. 2006 Apr;25(4):516-20.
The ras family of proto-oncogenes are upstream mediators of several essential cellular signal transduction pathways involved in cell proliferation and survival. Point mutations of ras oncogenes result in constitutive activation of oncogenic Ras. The key step in post-translational processing of Ras protein is farnesylation by farnesyl transferase. Inhibitors of this enzyme were developed initially as a therapeutic strategy for Ras-mutated tumors. Moreover, it is now clear that farnesyl transferase inhibitors (FTIs) have activity independent of Ras, and show some effects on tumors without oncogenic ras mutations. Preclinical data show that FTIs can inhibit proliferation of breast cancer cells in vitro and in vivo, and phase II studies of FTI-R115777 in advanced breast cancer show encouraging results. Therefore, FTIs, used alone or with other agents, may be a novel therapeutic approach for breast cancer.
原癌基因ras家族是参与细胞增殖和存活的几种重要细胞信号转导途径的上游介质。ras癌基因的点突变导致致癌性Ras的组成性激活。Ras蛋白翻译后加工的关键步骤是法尼基转移酶进行的法尼基化。该酶的抑制剂最初被开发作为Ras突变肿瘤的治疗策略。此外,现在很清楚,法尼基转移酶抑制剂(FTIs)具有独立于Ras的活性,并且对没有致癌性ras突变的肿瘤也有一些作用。临床前数据表明,FTIs在体外和体内均可抑制乳腺癌细胞的增殖,并且FTI-R115777在晚期乳腺癌中的II期研究显示出令人鼓舞的结果。因此,单独使用或与其他药物联合使用的FTIs可能是一种治疗乳腺癌的新方法。