Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma.

Area of Science:

• Oncology
• Exercise Physiology
• Cancer Biology

Background:

• Exercise enhances tumor vascular function and chemotherapy delivery in some cancers.
• Mechanisms and effects on Ewing sarcoma (ES) remain unclear.
• Exercise's impact on tumor vascular hyperpermeability, crucial for drug delivery, is unevaluated.

Purpose of the Study:

• To investigate if exercise improves chemotherapy efficacy in Ewing sarcoma by enhancing drug delivery.
• To determine the effect of exercise on tumor vascular hyperpermeability and associated mechanisms in ES.

Main Methods:

• ES-bearing mice were treated with doxorubicin, with or without moderate treadmill exercise.
• Tumor vascular morphology, hyperpermeability, hypoxia, and doxorubicin penetration were assessed.
• Expression of sphingosine-1-phosphate receptors 1 and 2 (S1PR1 and S1PR2) in endothelial cells was evaluated.

Main Results:

• Exercise did not alter ES tumor vessel morphology but significantly reduced hyperpermeability and hypoxia.
• Doxorubicin penetration into tumors was higher in exercised mice.
• Doxorubicin plus exercise inhibited tumor growth more effectively than doxorubicin alone.
• Exercise increased S1PR1 and decreased S1PR2 expression in tumor vessels.

Conclusions:

• Exercise remodels ES vasculature to reduce hyperpermeability, potentially via S1PR1/S1PR2 modulation.
• This improves doxorubicin delivery and enhances anti-tumor efficacy.
• Moderate aerobic exercise warrants investigation as an adjuvant therapy for ES patients.