Aerobic exercise remodels tumor vasculature to improve drug delivery and enhance treatment response in cancer.

Structural and functional abnormalities of tumor vasculature are key factors limiting drug delivery and therapeutic efficacy. This review aims to systematically summarize the mechanisms and evidence regarding how aerobic exercise improves drug delivery and enhances tumor treatment response by remodeling tumor vascular function. By synthesizing recent studies, we summarize the effects of different aerobic exercise modalities (intensity, duration, frequency) on tumor vasculature and the synergistic effects of combining exercise with pharmacotherapy. Aerobic exercise can increase pericyte coverage and enhance vascular stability, reduce vascular permeability and tumor interstitial fluid pressure (IFP) to improve drug penetration, enhance tumor blood flow perfusion and oxygenation to alleviate the hypoxic microenvironment, and modulate tumor metabolism and acid-base balance. These effects collectively promote the distribution and accumulation of drugs within tumor tissue, thereby enhancing treatment efficacy. The effects of exercise are influenced by its intensity, duration, frequency, and tumor type, with moderate-intensity, regular regimens (e.g., 3–5 times per week) being the most substantiated. Aerobic exercise serves as an effective non-pharmacological adjuvant that can significantly improve drug delivery and enhance anti-tumor treatment outcomes through multi-dimensional remodeling of tumor vascular function and the tumor microenvironment. Future prospective clinical studies, incorporating imaging and molecular biomarkers, are needed to further define optimal exercise protocols and their role in individualized integrated cancer therapy.