[Cell cycle-targeted therapy].

Abstract

BACKGROUND: The cell cycle defines sequential molecular processes that ensure orderly cell division. The progression throughout the cell cycle is governed by cyclin-dependent kinases, each of which is enzymatically active solely upon binding to its specific cyclin. The cell cycle harbours two checkpoints, or surveillance posts, which are activated when DNA is damaged. The response to the DNA damage involves a temporary cell cycle arrest, mediated by cell cycle inhibitors or other enzyme proteins, ultimately leading to the outcome of cell survival if the DNA is properly repaired, or cell death. The cell cycle checkpoints may also be biological targets for new therapeutic strategies in cancer intervention. MATERIAL AND METHODS: We compared the effect of ionising radiation on tumour cells with intact or defective functions of the cell cycle checkpoint that governs cell division. RESULTS: The tumour cells responded to radiation-induced DNA damage by cell cycle arrest that required intact checkpoint function. This defence response was overridden upon treatment of the tumour cells with a checkpoint signalling inhibitor. INTERPRETATION: Several pharmacological compounds designed to experimentally target the cell cycle are currently in the pipeline for testing in early-phase clinical trials and may have therapeutic potential as radiosensitizers.