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Thalidomide radiosensitizes tumors through early changes in the tumor microenvironment
Réginald Ansiaux1, Christine Baudelet, Bénédicte F Jordan
1Laboratories of Biomedical Magnetic Resonance, Université Catholique de Louvain, Avenue E. Mounier 73-40, B-1200 Brussels, Belgium.
Summary
Thalidomide treatment normalized tumor vasculature, increasing oxygenation and improving radiotherapy effectiveness. These microenvironmental changes occurred within two days, enhancing tumor radiosensitization.
Area of Science:
- Oncology
- Cancer Biology
- Radiotherapy
Background:
- Antiangiogenic therapies target tumor vasculature.
- Thalidomide is an angiogenesis inhibitor with potential in cancer treatment.
- Tumor microenvironment characteristics influence treatment response.
Purpose of the Study:
- To investigate early changes in the tumor microenvironment following thalidomide treatment.
- To assess the potential of thalidomide-induced vascular normalization to enhance radiotherapy.
- To focus on the impact of thalidomide on tumor vasculature and oxygenation.
Main Methods:
- Studied tumor oxygenation, perfusion, permeability, interstitial fluid pressure (IFP), and radiation sensitivity in an FSAII tumor model.
- Administered thalidomide (200 mg/kg daily) to mice.
- Utilized electron paramagnetic resonance oximetry for oxygen measurements, dynamic contrast-enhanced MRI, Patent Blue staining, and laser Doppler imaging for perfusion assessment, and wick-in-needle technique for IFP.
Main Results:
- Thalidomide treatment led to significant tumor reoxygenation within two days.
- Observed correlated reductions in IFP and increases in tumor perfusion.
- Vascular remodeling, confirmed by CD31 labeling, underlies these observed changes.
Conclusions:
- Thalidomide-induced microenvironmental modifications effectively radiosensitized tumors.
- Radiosensitization was observed in vivo but not in vitro, suggesting a role for the tumor microenvironment.
- The findings suggest that initial vascular normalization by thalidomide is key to tumor radiosensitization within a specific time window.