A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial

Smith, Tim A.D.; West, Catharine M.L.; Joseph, Nuradh; Lane, Brian; Irlam-Jones, Joely; More, Elisabet; Mistry, Hitesh; Reeves, Kimberley J.; Song, Yee Pei; Reardon, Mark; Hoskin, Peter J.; Hussain, Syed A.; Denley, Helen; Hall, Emma; Porta, Nuria; Huddart, Robert A.; James, Nick D.; Choudhury, Ananya

doi:10.1016/j.ebiom.2024.105032

Cited by 2 publications

(2 citation statements)

References 37 publications

(57 reference statements)

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“…Like EBRT, the response of the tumour is dependent on the cancer cell’s intrinsic radiosensitivity and microenvironmental factors, particularly O 2 level [ 4 ]. Hypoxic tumours are known to be radioresistant and sensitive to a radiotherapy fractionation regimen, which can be resolved by hypoxia modification [ 5 , 6 ]. Gene expression-based biomarkers of hypoxia have been extensively validated in multiple cohorts of patients undergoing EBRT, predicting prognosis and benefit of hypoxia modification [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Hypoxic tumours are known to be radioresistant and sensitive to a radiotherapy fractionation regimen, which can be resolved by hypoxia modification [ 5 , 6 ]. Gene expression-based biomarkers of hypoxia have been extensively validated in multiple cohorts of patients undergoing EBRT, predicting prognosis and benefit of hypoxia modification [ 6 ]. Transcriptomic biomarkers of intrinsic radiosensitivity have also been validated in the photon EBRT setting in patient cohorts [ 7 ] but fully validated gene expression signatures for MRT are limited.…”

Section: Introductionmentioning

confidence: 99%

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Gene Abnormalities and Modulated Gene Expression Associated with Radionuclide Treatment: Towards Predictive Biomarkers of Response

Smith

2024

Genes

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Molecular radiotherapy (MRT), also known as radioimmunotherapy or targeted radiotherapy, is the delivery of radionuclides to tumours by targeting receptors overexpressed on the cancer cell. Currently it is used in the treatment of a few cancer types including lymphoma, neuroendocrine, and prostate cancer. Recently reported outcomes demonstrating improvements in patient survival have led to an upsurge in interest in MRT particularly for the treatment of prostate cancer. Unfortunately, between 30% and 40% of patients do not respond. Further normal tissue exposure, especially kidney and salivary gland due to receptor expression, result in toxicity, including dry mouth. Predictive biomarkers to select patients who will benefit from MRT are crucial. Whilst pre-treatment imaging with imaging versions of the therapeutic agents is useful in demonstrating tumour binding and potentially organ toxicity, they do not necessarily predict patient benefit, which is dependent on tumour radiosensitivity. Transcript-based biomarkers have proven useful in tailoring external beam radiotherapy and adjuvant treatment. However, few studies have attempted to derive signatures for MRT response prediction. Here, transcriptomic studies that have identified genes associated with clinical radionuclide exposure have been reviewed. These studies will provide potential features for seeding multi-component biomarkers of MRT response.

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