How do we find better radiosensitizers

The hypoxic cell radiosensitizer, misonidazole, currently in trial, is neurotoxic, and this limits its clinical applicability. The development of new sensitizers with improved therapeutic ratio depends on identifying the chemical and structural properties associated with neurotoxicity or increasing the sensitization efficiency without increasing this neurotoxicity. The paper discusses firstly some current approaches aimed at reducing neurotoxicity, including the study of the possible relevance of lipophilic properties and, secondly, methods for increasing drug efficiency. The latter includes exploitation of the electron-affinity relationship, the synthesis of compounds with both sensitizing and alkylating activity, the study of an unusual series of super-active sensitizers and exploration of non-nitro-containing electron-affinic compounds