Strategies for the analysis of invitro radiation sensitivity and prediction of interaction with potential radiation modifying agents

Purpose: To better predict radiationdrug interactions in invitro model systems, thorough assessment of the effects of invitro exposure is required. The aim of this article is to show that both clonogenic capacity and cellular proliferation, which represent important different elements of tumour conduct, can be considered when assessing invitro radio sensitisation. Methods:A model was designed that can predict radiationdrug interactions based on changes in clonogenic capacity and cell proliferation by radiation modifying agents. Results:Using this mechanistical model, the effect of combined exposure to radiation and potential drugs can be tested on both established cell lines and primary cells. In addition, we could obtain more information about the mechanisms underlying the radiationdrug interaction by assessing the results of invitro exposure on tumour cell proliferation and clonogenic capacity according to our model. Conclusions:The significance of our model is not to replace the clonogenic gold standard but to give additional information about the radiationdrug combination by determining cell proliferation. Moreover, the advantage is that the interaction can also be predicted in cases where a clonogenic assay is not possible. Additional research into the biological effect of potential radio-sensitisers is warranted for future (pre)clinical studies.