Integrative radiation systems biology

Kristian Unger

doi:10.1186/1748-717x-9-21

Abstract

Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer” of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology.

Highlights

Why we need to improve radiation therapy Radiation therapy is beside chemo-/immunotherapy and surgery part of the standard treatment of many cancers
In the context of radiation therapy, individual radiation sensitivity seems to be the key feature of tumours and its understanding needs to be addressed when it comes to efforts of improving the efficiency of radiotherapy
The overall prerequisite for improving the long-term efficiency of raditoherapy is a deep understanding of the underlying mechanisms of radiation sensitivity in tumour cells in order to get a handle on the control of this phenomenon

Summary

Introduction

Why we need to improve radiation therapy Radiation therapy is beside chemo-/immunotherapy and surgery part of the standard treatment of many cancers. The mechanisms governing radiation resistance are not fully understood there are already some radiotherapy concomitant treatment options that have made it into clinics that target important signalling pathways or the cells surrounding the tumour that are known to have an impact on the radiation sensitivity.

Results

Conclusion