Biological Predictors of Response to Radiotherapy in Head and Neck Cancer: Recent Advances and Emerging Perspectives

The study of new biological parameters has received considerable attention in radiotherapy during the last decade due to their potential value in predicting treatment response in squamous cell carcinoma of the head and neck (SCC-HN) and the foreseen possibility of selecting altered fractionation radiotherapy for the individual patient. Although there are established clinical parameters in SCC-HN patients that relate to radiation response (extent of disease, hemoglobin level), recent advances with direct measurement of tumor oxygenation, inherent radiosensitivity and proliferation rate have increased the promise of individualization of treatment strategy according to these radiobiologically based parameters. Molecular research has now identified a host of new biological parameters with potential predictive utility; oncogenes, tumor suppressor genes, cell-cycle control genes, apoptosis genes and angiogenesis genes have been extensively studied and correlated with radiation response. Moreover, study of the epidermal growth factor receptor signal-transduction system as a possible response modulator has recently fostered molecular strategies which employ blockade of the receptor to down-regulate tumor growth. This article briefly reviews and analyzes the main controversial issues and drawbacks that hinder the general use of biological parameters for predicting tumor response to radiotherapy. It highlights the future perspectives of radiotherapy predictive assay research and the need to shift from single-parameter analysis to multiparametric studies which take into account several potential predictors that together are involved in different biological and clinical pathways.