title: Defining molecular and cellular responses after low and high linear energy transfer radiations to develop biomarkers of carcinogenic risk or therapeutic outcome.
abstract: The variability in radiosensitivity across the human population is governed in part by genetic factors. The ability to predict therapeutic response, identify individuals at greatest risk for adverse clinical responses after therapeutic radiation doses, or identify individuals at high risk for carcinogenesis from environmental or medical radiation exposures has a medical and economic impact on both the individual and society at large. As radiotherapy incorporates particles, particularly particles larger than protons, into therapy, the need for such discriminators, (i.e., biomarkers) will become ever more important. Cellular assays for survival, DNA repair, or chromatid/chromosomal analysis have been used to identify at-risk individuals, but they are not clinically applicable. Newer approaches, such as genome-wide analysis of gene expression or single nucleotide polymorphisms and small copy number variations within chromosomes, are examples of technologies being applied to the discovery process. Gene expression analysis of primary or immortalized human cells suggests that there are distinct gene expression patterns associated with radiation exposure to both low and high linear energy transfer radiations and that those most radiosensitive are discernible by their basal gene expression patterns. However, because the genetic alterations that drive radio response may be subtle and cumulative, the need for large sample sizes of specific cell or tissue types is required. A systems biology approach will ultimately be necessary. Potential biomarkers from cell lines or animal models will require validation in a human setting where possible and before being considered as a credible biomarker some understanding of the molecular mechanism is necessary.
authors.affiliation: Department of Radiation Oncology, Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. michael.story@utsouthwestern.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Story
authors.forename: Liang-hao
authors.initials: LH
authors.lastname: Ding
authors.forename: William A
authors.initials: WA
authors.lastname: Brock
authors.forename: K Kian
authors.initials: KK
authors.lastname: Ang
authors.forename: Ghazi
authors.initials: G
authors.lastname: Alsbeih
authors.forename: John
authors.initials: J
authors.lastname: Minna
authors.forename: Seongmi
authors.initials: S
authors.lastname: Park
authors.forename: Amit
authors.initials: A
authors.lastname: Das
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D018499:Linear Energy Transfer; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D011836:Radiation Tolerance / Q000528:radiation effects*; D012306:Risk; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor