Ionizing radiation is used to treat about 65% of U.S. cancer patients. A better understanding of agents, which affect cell killing by radiation, is needed, particularly at doses used in the clinic. Since many patients will also have chemotherapy, the interactions between the two modalities also require better understanding, at clinically relevant doses and concentrations.
A basic paradigm in radiobiology is that the effects of ionizing radiation on mammalian cells measured at relatively high doses can be extrapolated to dose regions of clinical interest. A recent discovery of hyper-radiosensitivity (HRS) and bystander effects (BSE) has caused us to reevaluate this central dogma. A consequence of HRS is a non-linear dose-dependent radiosensitivity and the enhancing rather than sparing effect of dose fractionation with doses 20-50 cGy/fraction.
Our model of HRS involves signal transduction pathways, largely independent of TP53 status, and results to date suggest that HRS is a G2/M phenomenon. This is interesting basic science, but has also clinical consequences. One aspect is the enhancement of HRS by microtubules-targeting anti-cancer drugs. Other aspects include the radiation response of normal tissue and possible consequences. For example, the possibility that there could be HRS in the penumbra, which would lead t more significant responses in irradiated tissues, certainly bear consideration. Finally, the area of HRS of relevance to the clinic has to do with its potential application in predictive assays.
