G1/S control and its deregulation in cancer

Excerpt

Cancer is increasingly viewed as a cell-cycle disease, a notion supported by recent accumulation of data on the molecular basis of the cell-cycle machinery and its defects commonly found in human tumours including breast carcinomas. Strikingly, the cell-cycle phase targeted most frequently in multistep oncogenesis is the control of G1/S transition. This period includes the late-G1 commitment to replicate the genome and complete the cycle (the restriction point control), and the initiation of DNA replication, events regulated by the so-called `RB pathway'. While the key components of the RB pathway qualify as proto-oncogenes or tumour suppressors, and their aberrations may provide direct proliferative advantage to cancer cells, defects in the so-called checkpoint mechanisms that monitor and help ensure the error-free execution of the cell-cycle transitions act more indirectly, yet affect both tumour progression and response to anti-cancer therapy. …