Cyclin-dependent kinases (cdks) and the DNA damage response: rationale for cdk inhibitor-chemotherapy combinations as an anticancer strategy for solid tumors.

摘要: Importance of the field: The eukaryotic cell division cycle is a tightly regulated series events coordinated by periodic activation multiple cyclin-dependent kinases (cdks). Small-molecule cdk-inhibitory compounds have demonstrated preclinical synergism with DNA-damaging agents in solid tumor models. An improved understanding how cdks regulate DNA damage response now provides an opportunity for optimization combinations cdk inhibitors and damaging chemotherapy that can be translated to clinical settings. Areas covered this review: Here, we discuss novel work uncovering roles DNA-damage-response network. First, they activate checkpoint repair pathways. Later their activity turned off, resulting arrest, allowing time occur. Recent data on inhibitor–DNA-damaging agent are also discussed. What reader will gain: Readers learn about areas biology, co...