Tumor vasculature remodeling by radiation therapy increases doxorubicin distribution and efficacy.

Abstract

The tumor microenvironment regulates cancer initiation, progression and response to treatment. In particular, the immature tumor vasculature may impede drugs from reaching tumor cells at a lethal concentration. We and others have shown that radiation therapy (RT) induces pericyte recruitment, resembling vascular normalization. Here, we asked whether radiation-induced vascular remodeling translates into improved tissue distribution and efficacy of chemotherapy. First, RT induced vascular remodeling, accompanied by decreased hypoxia and/or increased Hoechst perfusion in prostate PC3 and LNCaP and Lewis lung carcinoma. These results were independent of the RT regimen, respectively 10 × 2 Gy and 2 × 12 Gy, suggesting a common effect. Next, using doxorubicin as a fluorescent reporter, we observed that RT improves intra-tumoral chemotherapy distribution. These effects were not hindered by anti-angiogenic sunitinib. Moreover, sub-optimal doses of doxorubicin had almost no effect alone, but significantly delayed tumor growth after RT. These data demonstrate that RT favors the efficacy of chemotherapy by improving tissue distribution, and could be an alternative chemosensitizing strategy.

• Authors: Vincent Potiron, Karen Clément-Colmou, Emmanuel Jouglar, Manon Pietri, Sophie Chiavassa, Grégory Delpon, François Paris, Stéphane Supiot
• Journal: Cancer letters (Cancer Lett) Vol. 457 Pg. 1-9 (08 10 2019) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 31078733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (metabolism, pharmacology)
• Carcinoma, Lewis Lung (blood supply, metabolism, pathology, therapy)
• Chemoradiotherapy
• Doxorubicin (metabolism, pharmacology)
• Female
• Humans
• Male
• Mice, Inbred C57BL
• Mice, Nude
• Neovascularization, Pathologic
• PC-3 Cells
• Prostatic Neoplasms (blood supply, metabolism, pathology, therapy)
• Radiation Dosage
• Tissue Distribution
• Tumor Burden (drug effects, radiation effects)
• Tumor Hypoxia
• Tumor Microenvironment
• Vascular Remodeling (radiation effects)
• Xenograft Model Antitumor Assays