Rowley P T, Tabler M
Department of Medicine and Division of Genetics, University of Rochester School of Medicine, Rochester, New York 14642, USA.
Anticancer Res. 2000 Nov-Dec;20(6B):4419-29.
Telomerase is attracting great interest as a target for anticancer research because telomerase activity is present in most malignant cells, but undetectable in most normal somatic cells. The antisense approach has been widely exploited and directed to telomerase RNA, chiefly the template region. Ribozymes have been less investigated. Agents that stabilize folded G-quadruplex structures also inhibit telomerase. Inhibitory agents from many chemical classes have been identified, many through screening, but their specificity of action is in doubt. A specific inhibitor is expected to immediately inhibit activity but not cell division, produce telomerase shortening over multiple generations, and ultimately produce end-to-end chromosomal fusion and growth arrest.
端粒酶作为抗癌研究的靶点正引起人们极大的兴趣，因为端粒酶活性存在于大多数恶性细胞中，而在大多数正常体细胞中却检测不到。反义方法已被广泛应用于端粒酶RNA，主要是模板区域。核酶的研究较少。稳定折叠的G-四链体结构的试剂也能抑制端粒酶。已鉴定出许多化学类别的抑制剂，其中许多是通过筛选得到的，但它们的作用特异性值得怀疑。一种特异性抑制剂有望立即抑制活性但不影响细胞分裂，在多代细胞中使端粒酶缩短，并最终导致染色体端对端融合和生长停滞。
