Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Clin Cancer Res. 2010 Feb 15;16(4):1094-9. doi: 10.1158/1078-0432.CCR-09-0787. Epub 2010 Feb 9.
The RB-pathway, consisting of inhibitors and activators of cyclin-dependent kinases, the retinoblastoma tumor suppressor (RB), and the E2F-family of transcription factors, plays critical roles in the regulation of cell cycle progression and cell death. Components of this pathway, particularly p16Ink4a, cyclin D1, and RB, are frequently altered in sporadic human cancers to promote deregulated cellular proliferation. The consistent disruption of the RB-pathway in human cancers raises the possibility of exploiting tumor-specific RB-pathway defects to improve the efficacy of current therapies and to develop new therapeutic strategies. This article discusses how the RB-pathway status impacts the cellular responses to cytotoxic, cytostatic, and hormone therapies, and how the components of the RB-pathway may be directly targeted to treat cancer.
RB 通路由细胞周期蛋白依赖性激酶的抑制剂和激活剂、视网膜母细胞瘤肿瘤抑制因子 (RB) 和 E2F 转录因子家族组成，在细胞周期进程和细胞死亡的调控中发挥着关键作用。该通路的组成部分，特别是 p16Ink4a、cyclin D1 和 RB，在散发性人类癌症中经常发生改变，以促进细胞增殖的失调。RB 通路在人类癌症中的持续破坏提出了利用肿瘤特异性 RB 通路缺陷来提高现有治疗方法的疗效并开发新的治疗策略的可能性。本文讨论了 RB 通路状态如何影响细胞对细胞毒性、细胞生长抑制和激素治疗的反应，以及 RB 通路的组成部分如何直接靶向治疗癌症。
