# Impact of Nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancer

## TL;DR

This study shows that Nintedanib reduces tumor growth and improves blood vessel structure in a mouse model of colorectal cancer.

## Contribution

The study demonstrates that Nintedanib induces vascular normalization and anti-tumor effects by inhibiting multiple pro-angiogenic pathways.

## Key findings

- Nintedanib significantly inhibited angiogenesis and reduced tumor growth in a colorectal cancer xenograft model.
- Treatment improved vascular structure and function, reducing leakage and enhancing oxygen delivery.
- The drug's effects suggest potential to improve the efficacy of existing cancer therapies like chemotherapy and radiation.

## Abstract

For many solid types of cancer including colorectal cancer treatment with the VEGF antibody bevacizumab as anti-angiogenic treatment has become standard of care. Nevertheless, long-term treatment with anti-angiogenic drugs in combination with other treatment modalities or alone can induce resistance through alternative pro-angiogenic pathways. In this study, we investigated the effects of nintedanib, an anti- VEGFR/PDGFR/FGFR kinase inhibitor, on tumor vasculature to determine the potential benefits of combined inhibition of multiple pro-angiogenic factors.

In a colorectal xenograft model, subcutaneous tumors were treated with Nintedanib. Tumor growth patterns were measured and tumors were analysed histologically regarding effects on tumor angiogenesis and parameters of vascular normalization.

Inhibition of VEGFR/PDGFR/FGFR by Nintedanib was able to reduce tumor growth by significantly inhibiting angiogenesis and inducing tumor cell death. The remaining vessels showed decreased vascular leakage and improved oxygen delivery, indicating a functionally and structurally improved vascular bed resulting from vascular normalization.

In xenograft mouse model of colorectal cancer Nintedanib revealed anti-tumoral effects and induced vascular normalization. Our findings indicate that the treatment with Nintedanib could be able to improve intratumoral oxygen and thereby drug delivery to potentially enhance the efficacy of preexisting oncological therapies such as chemotherapy and radiation.

The online version contains supplementary material available at 10.1007/s12672-025-03071-4.