Romaniuk Aleksandra, Kopczynski Przemyslaw, Ksiazek Krzysztof, Rubis Blazej
Poznan University of Medical Sciences, Department of Clinical Chemistry and Molecular Diagnostics, Przybyszewskiego 49 Str., 60-355 Poznan, Poland.
Curr Pharm Des. 2014;20(41):6438-51. doi: 10.2174/1381612820666140630092721.
Telomerase is a specialized enzymatic complex responsible for the synthesis of telomeric repeats 5'-TTAGGG-3' localized at the ends of eukaryotic chromosomes. This mechanism prevents shortening of telomeres after each cell division. The enzyme is detected in about 85% of human tumors, but it is not expressed in normal cells or its expression is significantly lower. Consequently, it provides the cancer cells immortality. Thus, since showing cancer cell specificity (to a certain extent), the enzyme became a target for an adjuvant cancer therapy. So far, in vitro studies and preclinical studies seem to be promising. This work focuses on the pathways and mechanisms that are targeted in order to eliminate telomerase with consequence of cancer cell death. The anti-telomerase strategy may be beneficial especially in the context of sensitization of tumor cell to chemotherapeutic agents. We also indicate potential side effects and consequences of telomerase downregulation that should be considered when anti-telomerase strategy is undertaken. Alternatively, we also emphasize potential useful application of telomerase induction.
端粒酶是一种特殊的酶复合物，负责合成位于真核染色体末端的端粒重复序列5'-TTAGGG-3'。这种机制可防止每次细胞分裂后端粒缩短。该酶在约85%的人类肿瘤中被检测到，但在正常细胞中不表达或其表达显著较低。因此，它赋予癌细胞永生性。因此，由于在一定程度上显示出癌细胞特异性，该酶成为辅助癌症治疗的靶点。到目前为止，体外研究和临床前研究似乎很有前景。这项工作聚焦于为消除端粒酶并导致癌细胞死亡而靶向的途径和机制。抗端粒酶策略可能特别有益于使肿瘤细胞对化疗药物敏感化。我们还指出了在实施抗端粒酶策略时应考虑的端粒酶下调的潜在副作用和后果。另外，我们也强调了端粒酶诱导的潜在有用应用。
