[Perspectives in biological modulation of radiotherapy]

Although the term "targeted therapy" is used to described new molecular approaches derived from the recent increase in the knowledge of cancer biology, radiation therapy is a "targeted therapy" used against cancer. Dose fractionation changes and time treatment duration modifications are used to specifically increase the anti tumor effects of ionising radiation while minimising normal tissue impact of these changes. The implementation of 3 dimensional radiation therapy and IMRT allowed specific tumor targeting and tumor radiation dose increase with normal tumor surrounding tissue relative protection. Clinical research has widely used those concepts with the development of hyper fractionation which showed positive results for head and neck tumours in clinical trials. The development of IMRT has allowed tumor dose escalation in the case of prostate cancer without significant increase in normal tissue toxicity. Beside these approaches, a better understanding of cancer biology and in particular of tumor radiation resistance mechanisms led to the identification of new molecular targets that could be used to increase the therapeutic ratio of radiation therapy. These approaches attempt to widen the therapeutic ratio of radiation, i.e. to increase specifically tumor radiation response with little impact on normal tissue response.