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Radioresistant tumours: From identification to targeting
É Cohen-Jonathan-Moyal1, V Vendrely2, L Motte3
1Department of radiation oncology, institut Claudius-Regaud, IUCT-O, 1, avenue Irène-Joliot-Curie, 31059 Toulouse cedex 9, France; Inserm UMR 1037, 1, avenue Irène-Joliot-Curie, 31059 Toulouse cedex 9, France; Centre de recherches en cancérologie de Toulouse, 1, avenue Irène-Joliot-Curie, 31059 Toulouse cedex 9, France.
Abstract:
From surviving fraction to tumour curability, definitions of tumour radioresistance may vary depending on the view angle. Yet, mechanisms of radioresistance have been identified and involve tumour-specific oncogenic signalling pathways, tumour metabolism and proliferation, tumour microenvironment/hypoxia, genomics. Correlations between tumour biology (histology) and imaging allow theragnostic approaches that use non-invasive biological imaging using tracer functionalization of tumour pathway biomarkers, imaging of hypoxia, etc. Modelling dose prescription function based on their tumour radio-resistant factor enhancement ratio, related to metabolism, proliferation, hypoxia is an area of investigation. Yet, the delivery of dose painting by numbers/voxel-based radiotherapy with low lineal energy transfer particles may be limited by the degree of modulation complexity needed to achieve the doses needed to counteract radioresistance. Higher lineal energy transfer particles or combinations of different particles, or combinations with drugs and devices such as done with radioenhancing nanoparticles may be promising.
Insights
Tumour radioresistance mechanisms involve complex biological factors. Advanced imaging and novel radiotherapy approaches, including high-energy particles and nanoparticles, show promise for overcoming treatment resistance.
Area of Science:
- Oncology
- Radiation Oncology
- Medical Imaging
Background:
- Tumour radioresistance is a complex challenge in radiation oncology, influenced by various biological factors.
- Mechanisms include oncogenic signaling, metabolism, proliferation, tumor microenvironment (hypoxia), and genomics.
- Understanding these factors is crucial for improving radiotherapy outcomes.
Purpose of the Study:
- To review the multifaceted mechanisms of tumour radioresistance.
- To explore theragnostic approaches linking tumour biology and imaging.
- To discuss advanced radiotherapy strategies for overcoming radioresistance.
Main Methods:
- Literature review of tumour radioresistance mechanisms.
- Discussion of theragnostic applications using biological imaging and biomarkers.
- Analysis of dose prescription modeling and advanced particle therapy techniques.
Main Results:
- Identified key mechanisms of radioresistance: oncogenic pathways, metabolism, hypoxia, and genomics.
- Highlighted the potential of theragnostic approaches correlating tumour histology with imaging.
- Investigated dose painting strategies and limitations of low lineal energy transfer particles.
Conclusions:
- Overcoming tumour radioresistance requires a comprehensive understanding of its underlying biological mechanisms.
- Theranostic imaging and advanced radiotherapy techniques, such as high lineal energy transfer particles or nanoparticles, offer promising avenues for enhancing tumour curability.
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