Preclinical models for cell cycle-targeted therapies

摘要: Deregulation of the cell cycle machinery is frequently associated to tumor development in most types. Many these tumor-associated alterations result abnormal activation cyclin-dependent protein kinases (Cdks) involved G1/S transition. Recent results from genetic analysis cyclins and Cdks mouse models have raised some questions regarding relevance molecules cycle-targeted strategies for cancer therapy. The comprehensive evaluation biochemical data seems be a necessary given other new as targets therapeutic approaches cancer. Cell progression controlled by diverse mechanisms including gene expression phosphorylation or degradation. Progression through G1 mostly genes required replication genome (S phase) chromosome segregation mitosis (M phase). later phases requires appropriate posttransla- tional modification existing proteins degradation when they are not an obstacle transition following phases. In last few years, examination Cdks, their regulators (cyclins Cdk inhibitors, CKIs) substrates (mainly retinoblastoma protein, pRb) has provided general framework under- standing how mammalian regulated. During phase cycle, cells may decide whether stay quiescent enter