Radiotherapy is the most widely used treatment for cancer and is administered to 50-60% of cancer patients. Drugs which sensitize tumour cells to ionizing radiation are potentially a very effective means to improve radiotherapy. DNA is the most important target for the lethal action of ionizing radiation; DNA crosslinks and DNA double strand breaks are very difficult for cells to repair and often lead to cell death. Thus, an effective strategy to sensitize cells to radiation is to use a radiosensitizer which increases the formation of lesions which are refractory to repair. We plan to develop radiosensitizers which target DNA, based on Peptide Nucleic Acids (PNA). PNA are remarkable molecules which are resistant to degradation in the body and which can invade specific sequences in the DNA of living cells. We have recently found that PNA form crosslinks with DNA with high efficiency when irradiated, suggesting that we should evaluate their potential as radiosensitizers.