Telomerase as a novel and potentially selective target for cancer chemotherapy
Telomerase as a novel and potentially selective target for cancer chemotherapy
复制标题
DOI：
10.1080/07853890310006361
复制
发表时间：
2003-01-01
影响因子：
4.4
通讯作者：
Parkinson, EK
中科院分区：
文献类型：
--
作者：
Parkinson, EK
端粒是保护真核生物染色体免受DNA损伤监视机制识别的结构，并通过端粒酶维持在多细胞动物的生殖系中。在大多数人类体细胞中，端粒酶在发育过程中沉默，并且在广泛的细胞分裂后，端粒缩短以触发生长停滞。大约80%的人类癌症通过重新激活端粒酶来逃避这种生长停滞，但在诊断时，许多癌症仍然具有非常短的端粒，使得它们非常容易受到端粒酶抑制的影响。由于正常细胞具有相当大的端粒储备，即使在老年人中，这使得端粒酶成为一个有吸引力的和潜在的选择性抗癌药物靶点。原则的验证实验进行审查表明，这种乐观可能是有道理的，至少对人类癌症的端粒短的子集。我还解决了许多普遍提出的关注，围绕端粒酶作为抗癌药物设计的目标。
Telomeres are the structures that protect eukaryotic chromosomes from recognition by DNA damage surveillance mechanisms and are maintained in the germ line of multicellular animals by telomerase. In most human somatic cells telomerase is silenced during development and after extensive cell division telomeres shorten to trigger growth arrest. Around 80% of human cancers escape from this growth arrest by re-activating telomerase but at diagnosis many cancers still have very short telomeres making them very vulnerable to the inhibition of telomerase. As normal cells have a considerable telomere reserve, even in elderly humans, this makes telomerase an attractive and potentially selective anti-cancer drug target. Proof-of-principle experiments are reviewed which show that this optimism may be justified at least for the subset of human cancers with short telomeres. I also address many of the commonly raised concerns that surround telomerase as a target for anti-cancer drug design.