Precision Radiation Oncology: Molecular Strategies to Enhance Anti-Tumour Responses to Radiotherapy—Beyond Direct Tumour Cell Killing
- 1The Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK
- 2The Institute of Cancer Research, London SW7 3RP, UK
Abstract
Radiotherapy remains a cornerstone of cancer treatment, yet treatment response continues to be limited by tumour radioresistance and considerable biological heterogeneity. Although advances in radiation delivery have substantially improved dose conformity and reduced toxicity, increasing evidence suggests that optimising therapeutic outcomes will require greater integration of tumour biology into treatment strategies. This review examines emerging molecular approaches that seek to enhance anti-tumour responses to radiotherapy beyond direct tumour cell killing. We discuss the DNA damage response as a therapeutic target for radiosensitisation, highlighting the evolving role of DNA damage response inhibitors in promoting both tumour cytotoxicity and immune activation. We further examine the mechanisms linking radiation-induced DNA damage to anti-tumour immunity, including immunogenic cell death, cGAS–STING signalling, and remodelling of the tumour microenvironment, together with the opportunities and challenges of combining radiotherapy with immune checkpoint inhibition. Finally, we review emerging concepts in precision radiation oncology, including spatially tailored irradiation strategies, genomically informed radiation prescription, radiogenomics, and the influence of the gut microbiome on treatment response. Collectively, these advances support a shift from anatomically guided radiotherapy towards biologically personalised treatment, integrating molecular, immunological and genomic information with normal-tissue susceptibility to improve the therapeutic ratio and enable more precise, patient-centred cancer care.
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BibTeX
@article{patel2026precision,
title = {{Precision Radiation Oncology: Molecular Strategies to Enhance Anti-Tumour Responses to Radiotherapy—Beyond Direct Tumour Cell Killing}},
author = {Vishit Patel and Asmita Raja and Madeha Khan and Alan A. Melcher and Irene Chong and Adam Young},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219396},
url = {https://www.mdpi.com/1422-0067/27/21/9396},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Precision Radiation Oncology: Molecular Strategies to Enhance Anti-Tumour Responses to Radiotherapy—Beyond Direct Tumour Cell Killing
AU - Vishit Patel
AU - Asmita Raja
AU - Madeha Khan
AU - Alan A. Melcher
AU - Irene Chong
AU - Adam Young
PY - 2026
DA - 2026/10/22
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219396
UR - https://www.mdpi.com/1422-0067/27/21/9396
AB - Radiotherapy remains a cornerstone of cancer treatment, yet treatment response continues to be limited by tumour radioresistance and considerable biological heterogeneity. Although advances in radiation delivery have substantially improved dose conformity and reduced toxicity, increasing evidence suggests that optimising therapeutic outcomes will require greater integration of tumour biology into treatment strategies. This review examines emerging molecular approaches that seek to enhance anti-tumour responses to radiotherapy beyond direct tumour cell killing. We discuss the DNA damage response as a therapeutic target for radiosensitisation, highlighting the evolving role of DNA damage response inhibitors in promoting both tumour cytotoxicity and immune activation. We further examine the mechanisms linking radiation-induced DNA damage to anti-tumour immunity, including immunogenic cell death, cGAS–STING signalling, and remodelling of the tumour microenvironment, together with the opportunities and challenges of combining radiotherapy with immune checkpoint inhibition. Finally, we review emerging concepts in precision radiation oncology, including spatially tailored irradiation strategies, genomically informed radiation prescription, radiogenomics, and the influence of the gut microbiome on treatment response. Collectively, these advances support a shift from anatomically guided radiotherapy towards biologically personalised treatment, integrating molecular, immunological and genomic information with normal-tissue susceptibility to improve the therapeutic ratio and enable more precise, patient-centred cancer care.
SN - 1422-0067
ER -