Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity? Cancer Lett 2016 Nov 01;382(1):95-109
Date
10/22/2016Pubmed ID
26944314Pubmed Central ID
PMC5016239DOI
10.1016/j.canlet.2016.02.035Scopus ID
2-s2.0-84960185958 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
Adverse reactions in normal tissue after radiotherapy (RT) limit the dose that can be given to tumour cells. Since 80% of individual variation in clinical response is estimated to be caused by patient-related factors, identifying these factors might allow prediction of patients with increased risk of developing severe reactions. While inactivation of cell renewal is considered a major cause of toxicity in early-reacting normal tissues, complex interactions involving multiple cell types, cytokines, and hypoxia seem important for late reactions. Here, we review 'omics' approaches such as screening of genetic polymorphisms or gene expression analysis, and assess the potential of epigenetic factors, posttranslational modification, signal transduction, and metabolism. Furthermore, functional assays have suggested possible associations with clinical risk of adverse reaction. Pathway analysis incorporating different 'omics' approaches may be more efficient in identifying critical pathways than pathway analysis based on single 'omics' data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of RT patients characterised by different mechanisms. Thus 'omics' and functional approaches may synergise if they are integrated into radiogenomics 'systems biology' to facilitate the goal of individualised radiotherapy.
Author List
Herskind C, Talbot CJ, Kerns SL, Veldwijk MR, Rosenstein BS, West CMAuthor
Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Gene Expression ProfilingGenetic Markers
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomics
Humans
Phenotype
Polymorphism, Single Nucleotide
Proteomics
Radiation Dosage
Radiation Exposure
Radiation Injuries
Radiotherapy
Risk Assessment
Risk Factors
Systems Biology
Systems Integration