Levy R
Unité d'Onco-Hématologie, Hôpital Laennec, Paris.
Presse Med. 1995;24(15):725-9.
Ras genes are frequently activated in human tumours. The role of their product, the P21 proteins, in the transduction of the mitogenic signal makes them attractive targets for an anti-neoplastic therapy. The p21 ras proteins are linked to the plasma membrane and transformed into an active form for signal transmission. Their effect is to mediate the effects of growth factors. Two drug families, the Benzodiazepine peptidomimetics and the CAAX tetrapeptides which inhibit the farnesylation of P21-Ras proteins abolish the transforming properties of mutated P21. These promising drugs could rapidly have clinical applications. They have been shown to be highly active at precise concentrations on ras-transformed cells but at the same concentrations are not toxic for untransformed cells. They do not effect other similar enzyme systems within the cell, underlining their selective capacity. Theoretically anti-ras therapy could only suspend cell transformation although it might be possible that if given long enough, a lethal threshold could be reached.
Ras基因在人类肿瘤中经常被激活。其产物P21蛋白在有丝分裂信号转导中的作用，使其成为抗肿瘤治疗的有吸引力的靶点。p21 ras蛋白与质膜相连，并转化为活性形式以进行信号传递。它们的作用是介导生长因子的作用。两类药物，即苯二氮䓬肽模拟物和抑制P21-Ras蛋白法尼基化的CAAX四肽，消除了突变型P21的转化特性。这些有前景的药物可能很快会有临床应用。已证明它们在精确浓度下对ras转化细胞具有高活性，但在相同浓度下对未转化细胞无毒。它们不会影响细胞内其他类似的酶系统，突出了它们的选择性能力。理论上，抗ras治疗只能暂停细胞转化，尽管如果给药时间足够长，可能会达到致死阈值。
