Clinically relevant biomarkers in targeted radiotherapy

Three classic parameters have been recognized as predictors or biomarkers of radiation response: intrinsic radiosensitivity, degree of hypoxia and repopulation capacity of clonogenic cells during a course of fractionated radiation therapy. Although good functional assays exist to measure these tumor parameters, and their use has led to the understanding of factors affecting outcome after radiotherapy, their application in clinical practice is hampered by technical difficulties, the length of time needed to obtain results and the lack of prospective randomized clinical trials. Recently, with the progress in molecular biology, genome-wide screening methods have been used to look for genetic signatures that can distinguish between good and bad outcome after radiotherapy. One of the most promising candidates is the epidermal growth factor receptor which is overexpressed or mutated in a variety of malignancies, such lung and head and neck cancer. Inhibition of this receptor has led to radio-sensitization with the prolongation of median survival in several cancers. Since there is significant variability in the response of patients with the same disease to radiotherapy, it would be very valuable to be able to predict which patients would benefit from a molecularly targeted therapy administered with concomitant radiation in order to increase the response rate (and cure rate) of those patients with radioresistant tumors. Optimally, this assay should be able to provide results in an efficient and reproducible manner and detect tumor genetic mutations that would provide specificity to the intervention. One approach currently in clinical practice to overcome intrinsic radioresistance and repopulation is stereotactic body radiotherapy coupled with image-guided radiation, a highly precise and powerful form of radiation, allowing radiation oncologist to treat tumors with more aggressive biological doses of radiation without causing serious normal tissues injury.