Universität zu Köln

Wirsik, Naita M. ORCID: 0000-0003-1619-6354, Seeger, Jens M. ORCID: 0000-0002-3192-9192, Schmidt, Thomas ORCID: 0000-0002-7166-3675, Hilberg, Frank ORCID: 0000-0001-8925-7336, Fuchs, Hans F. ORCID: 0000-0003-4764-8050, Bruns, Christiane J. ORCID: 0000-0001-6590-8181, Coutelle, Oliver, Kashkar, Hamid ORCID: 0000-0003-2796-1429 and Schiffmann, Lars M. ORCID: 0000-0002-2320-5004 (2025). Impact of Nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancer. Discover Oncology, 16 (1). pp. 1-9. Springer Nature. ISSN 2730-6011

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Abstract

[Artikel-Nr. 1295] Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Wirsik, Naita M. UNSPECIFIED https://orcid.org/0000-0003-1619-6354 UNSPECIFIED Seeger, Jens M. UNSPECIFIED https://orcid.org/0000-0002-3192-9192 UNSPECIFIED Schmidt, Thomas UNSPECIFIED https://orcid.org/0000-0002-7166-3675 UNSPECIFIED Hilberg, Frank UNSPECIFIED https://orcid.org/0000-0001-8925-7336 UNSPECIFIED Fuchs, Hans F. UNSPECIFIED https://orcid.org/0000-0003-4764-8050 UNSPECIFIED Bruns, Christiane J. UNSPECIFIED https://orcid.org/0000-0001-6590-8181 UNSPECIFIED Coutelle, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, Hamid UNSPECIFIED https://orcid.org/0000-0003-2796-1429 UNSPECIFIED Schiffmann, Lars M. UNSPECIFIED https://orcid.org/0000-0002-2320-5004 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-802095
Identification Number:	10.1007/s12672-025-03071-4
Journal or Publication Title:	Discover Oncology
Volume:	16
Number:	1
Page Range:	pp. 1-9
Number of Pages:	9
Date:	10 July 2025
Publisher:	Springer Nature
ISSN:	2730-6011
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers Faculty of Medicine
Divisions:	Faculty of Medicine > Chirurgie > Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Transplantationschirurgie Faculty of Medicine > Weitere > Centrum für integrierte Onkologie (CIO) Faculty of Medicine > Weitere > Molekulare Immunologie
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80209