Brighenti Elisa, Treré Davide, Derenzini Massimo
Department of Experimental, Diagnostic and Specialty Medicine, Bologna University, Bologna, Italy.
Oncotarget. 2015 Nov 17;6(36):38617-27. doi: 10.18632/oncotarget.5775.
The effects of many chemotherapeutic drugs on ribosome biogenesis have been underestimated for a long time. Indeed, many drugs currently used for cancer treatment--and which are known to either damage DNA or hinder DNA synthesis--have been shown to exert their toxic action mainly by inhibiting rRNA synthesis or maturation. Moreover, there are new drugs that have been proposed recently for cancer chemotherapy, which only hinder ribosome biogenesis without any genotoxic activity. Even though ribosome biogenesis occurs in both normal and cancer cells, whether resting or proliferating, there is evidence that the selective inhibition of ribosome biogenesis may, in some instances, result in a selective damage to neoplastic cells. The higher sensitivity of cancer cells to inhibitors of rRNA synthesis appears to be the consequence of either the loss of the mechanisms controlling the cell cycle progression or the acquisition of activating oncogene and inactivating tumor suppressor gene mutations that up-regulate the ribosome biogenesis rate. This article reviews those cancer cell characteristics on which the selective cancer cell cytotoxicity induced by the inhibitors of ribosome biogenesis is based.
长期以来，许多化疗药物对核糖体生物合成的影响一直被低估。事实上，目前许多用于癌症治疗的药物——已知它们要么损伤DNA，要么阻碍DNA合成——已被证明主要通过抑制rRNA合成或成熟来发挥其毒性作用。此外，最近有一些新药被提议用于癌症化疗，它们仅阻碍核糖体生物合成，而没有任何基因毒性活性。尽管核糖体生物合成在正常细胞和癌细胞中都会发生，无论细胞处于静止还是增殖状态，但有证据表明，在某些情况下，对核糖体生物合成的选择性抑制可能会导致对肿瘤细胞的选择性损伤。癌细胞对rRNA合成抑制剂的更高敏感性似乎是由于控制细胞周期进程的机制丧失，或者是由于获得了激活癌基因和失活肿瘤抑制基因突变，从而上调了核糖体生物合成速率。本文综述了核糖体生物合成抑制剂诱导的选择性癌细胞细胞毒性所基于的那些癌细胞特征。
