[New strategies to interfere with radiation response: "biomodulation" of radiation therapy]

The development of several new anti cancer agents has been made possible because of recent significant achievements in our global understanding of cancer biology. These new "targeted" agents selectively inhibit targets necessary for tumor cell growth and viability with little toxicity to normal cells compared to conventional cytotoxic agents. So far, the efficacy of many of these new promising agents when used alone treatment remains limited, it is likely that the optimal use of these agents could be obtained in combination with conventional agents such as radiation therapy. The potential benefit of these targeted therapies combined with irradiation seems important. They might offer the advantage of increasing the tumor response to radiation with no or little increase in normal tissue damage. Therefore, these new types of chemo-radiation approaches might respect the normal tissue versus tumor cell "therapeutic ratio". These approaches can be sub divided in three sub groups: 1) Therapeutics targeting selectively one tumor related biochemical activity such as EGFR inhibitors. These approaches are efficient but one mutation of the target might render them inefficient. 2) Therapeutics directed against a widely expressed target. This is the case for anti Insulin Growth Factor-1 (IGF1R) interventions: IGF1R inhibition seems to specifically alter tumor cell viability with a minimal effect on normal cells viability. 3) Strategies which are not targeted against the tumor but the microenvironment, especially angiogenesis. This type of approaches seems to be applicable independently of tumor intrinsic biologic related factors.