Ataxia-telangiectasia mutated and the Mre11-Rad50-NBS1 complex: promising targets for radiosensitization.

摘要: Radiotherapy plays a central part in cancer treatment, and use of radiosensitizing agents can greatly enhance this modality. Although studies have shown that several chemotherapeutic the potential to increase radiosensitivity tumor cells, investigators also studied number molecularly targeted as radiosensitizers clinical trials based on reasonably promising preclinical data. Recent intense research into DNA damage-signaling pathway revealed ataxia-telangiectasia mutated (ATM) Mre11-Rad50-NBS1 (MRN) complex play roles repair cell cycle checkpoints these molecules are targets for radiosensitization. Researchers recently developed three ATM inhibitors (KU-55933, CGK733, CP466722) an MRN inhibitor (mirin) showed they great tumors preclinical studies. Additionally, we telomerase-dependent oncolytic adenovirus (OBP-301 [telomelysin]) produces profound effects by inhibiting via adenoviral E1B55kDa protein. A recent Phase I trial United States determined telomelysin was safe well tolerated humans, agent is about be tested combination with radiotherapy intriguing data demonstrating ionizing radiation potentiate each other. In review, highlight inhibitors, including telomelysin, agents.