法尼基转移酶抑制剂--乳腺癌新的治疗药物

原癌基因ras家族编码是与细胞增殖和生长有关的一些重要细胞信号途径的上游产物。ras基因突变导致Ras激活并具有致癌性。翻译后的Ras蛋白的关键环节是经法尼基转移酶的法尼基化。此酶的抑制剂首先被用于抑制Ras突变肿瘤的治疗。但现在发现法尼基转移酶抑制剂(farnesyltransferaseinhibitors,FTIs)还具有不依赖Ras的活性、对缺乏Ras突变的某些肿瘤的治疗也有效。基础资料显示FTIs可以抑制体内、外乳腺癌细胞的生长;Ⅱ期临床研究显示FTI-R115777对进展期乳腺癌的治疗有效。因此,FTIs单药或联合用药有可能成为乳腺癌治疗的新方法。

Farnesyl transferase inhibitors--a novel agent for breast cancer

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.