Owing to advances in radiotherapy, the physical properties of radiation can be optimized to enable individualized treatment; however, optimization is rarely based on biological properties and, therefore, treatments are generally planned with the assumption that all tumours respond similarly to radiation. Radiation affects multiple cellular pathways, including DNA damage, hypoxia, proliferation, stem cell phenotype and immune response. In this Review, we summarize the effect of these pathways on tumour responses to radiotherapy and the current state of research on genomic classifiers designed to exploit these variations to inform treatment decisions. We also discuss whether advances in genomics have generated evidence that could be practice changing and whether advances in genomics are now ready to be used to guide the delivery of radiotherapy alone or in combination.
The biological effects of radiation are mediated by a complex network of signalling pathways, and assessing these effects can help to classify tumours as radiosensitive or radioresistant.
Advances in genomics could be used to guide the delivery of radiotherapy alone and in combination; the commercialization of genomic-based tools will be important to drive their implementation.
Developments from the past 20 years have enabled unprecedented high-throughput analyses and rapid profiling of RNA and DNA that are currently embedded in clinical laboratories.
The community needs to learn from past failures to translate radiobiology biomarkers into the clinic and improve collaborations, focusing on standardizing methods and performing multicentre validation.
RNA-based signatures are among the most advanced tools currently available: a ten-gene signature of cellular radiosensitivity should be available soon, and hypoxia-related signatures need further testing in clinical trials.
The development of DNA-based signatures is currently in progress, and areas that need further study include the role of somatic mutations in DNA damage response genes that affect radiosensitivity.
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J.M.P. is supported by The Taylor Family Foundation. C.M.L.W. is supported by the Manchester NIHR Biomedical Research Centre.
C.M.L.W. is co-founder of ManTRa Diagnostics, which seeks to commercialize hypoxia-associated gene signatures. J.M.P. and A.P. declare no competing interests.
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Price, J.M., Prabhakaran, A. & West, C.M.L. Predicting tumour radiosensitivity to deliver precision radiotherapy. Nat Rev Clin Oncol 20, 83–98 (2023). https://doi.org/10.1038/s41571-022-00709-y