Gene Expression Studies for the Development of Particle Therapy.

Proton therapy for cancer is now in widespread use, and facilities for carbon ion therapy are showing great promise, but a more complete understanding of the mechanisms underlying particle radiation therapy is still needed in order to optimize treatment. Studies of gene expression, especially those using whole genome techniques, can provide insight into many of the questions still remaining, from the molecular mechanisms involved to predicting patient outcome. This review will summarize gene expression studies of response to proton and carbon ion beams, as well as high-energy protons and high-z high-energy particles with relevance to particle therapy. In general, most such studies find that, in comparison with x-ray or gamma-ray exposure, particle irradiation increases both the number of genes responding and the magnitude of the response. Patterns of gene expression have suggested impacts on specific pathways of relevance to radiation therapy, such as enhancement or suppression of tumor progression or metastasis. However, even within the relatively small number of studies done to date there is no clear consensus of response, suggesting influence by multiple parameters, such as particle type, particle energy, and tumor type. Systematic gene expression studies can help to address these issues, and promoting a culture of data sharing will expedite the process, benefiting investigators across the radiation therapy field.