Gene Expression Studies for the Development of Particle Therapy

Abstract

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.

High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells

“…Even though we also found several genes “unique” to a specific radiation type, it is likely that many of them would also respond to the other radiation types in a different experimental set-up (i.e. time-dose combination) due to the differences in RBE and\or gene expression kinetics, but what is already clear from our and other studies is that the magnitude of gene expression changes and the number of differentially expressed genes are consistently higher for high-LET particles ( 22 ). Some of the observed differences may be explained by the different nature of X-rays (photons) and heavy ions (particles).…”

“…Radiobiological transcriptional studies can offer valuable insight in this regard, revealing the biological basis of the cellular response to different radiation types ( 21 , 22 ). Peripheral blood is an easily-accessible biological sample which allows minimally invasive testing.…”

Influence of Therapeutic Proton Beam on Glioblastoma Multiforme Proliferation Index — A Preliminary Study

“…Authors showed that results are strongly influenced by the type of cells, culture condition, dose, dose rate, fractionation, and other physical features (i.e., LET, RBE) [22]. S.A. Amundson et al published that proton irradiation compared to X or gamma irradiation increases gene expression level in both their number and strength of response [23]. In the case of rat C6 glioblastoma, similar to human glioblastomas grade IV, the significant decrease in proliferation was found at a dose of 5 Gy and 10 Gy of X-rays after 48 h of culture [24].…”

Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts

“…Transcriptional profiling corresponds to the genes induced at these different dose levels. In general, at low doses, the genes induced are involved in general metabolism (bioenergetics and biosynthetic functions) whereas high doses activate genes involved in cell cycle arrest, DNA repair and apoptosis [ 182 , 183 ]. Even if these are not yet fully understood, they may well have a bearing on radioprotection and radiotherapeutic issues.…”