Impact of Nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancer
Abstract 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 c...
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| Format: | Article |
| Language: | English |
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Springer
2025-07-01
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| Series: | Discover Oncology |
| Online Access: | https://doi.org/10.1007/s12672-025-03071-4 |
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| author | Naita M. Wirsik Jens M. Seeger Thomas Schmidt Frank Hilberg Hans F. Fuchs Christiane J. Bruns Oliver Coutelle Hamid Kashkar Lars M. Schiffmann |
| author_facet | Naita M. Wirsik Jens M. Seeger Thomas Schmidt Frank Hilberg Hans F. Fuchs Christiane J. Bruns Oliver Coutelle Hamid Kashkar Lars M. Schiffmann |
| author_sort | Naita M. Wirsik |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-c74f07a8d3b34a4d9d5210e7759ecfc6 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-c74f07a8d3b34a4d9d5210e7759ecfc62025-08-20T03:42:57ZengSpringerDiscover Oncology2730-60112025-07-011611910.1007/s12672-025-03071-4Impact of Nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancerNaita M. Wirsik0Jens M. Seeger1Thomas Schmidt2Frank Hilberg3Hans F. Fuchs4Christiane J. Bruns5Oliver Coutelle6Hamid Kashkar7Lars M. Schiffmann8Department of General, Visceral, Thoracic and Transplant Surgery, University of CologneInstitute for Molecular Immunology, Faculty of Medicine and University Hospital of Cologne, University of CologneDepartment of General, Visceral, Thoracic and Transplant Surgery, University of CologneBoehringer Ingelheim RCVDepartment of General, Visceral, Thoracic and Transplant Surgery, University of CologneDepartment of General, Visceral, Thoracic and Transplant Surgery, University of CologneInstitute for Molecular Immunology, Faculty of Medicine and University Hospital of Cologne, University of CologneInstitute for Molecular Immunology, Faculty of Medicine and University Hospital of Cologne, University of CologneDepartment of General, Visceral, Thoracic and Transplant Surgery, University of CologneAbstract 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.https://doi.org/10.1007/s12672-025-03071-4 |
| spellingShingle | Naita M. Wirsik Jens M. Seeger Thomas Schmidt Frank Hilberg Hans F. Fuchs Christiane J. Bruns Oliver Coutelle Hamid Kashkar Lars M. Schiffmann Impact of Nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancer Discover Oncology |
| title | Impact of Nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancer |
| title_full | Impact of Nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancer |
| title_fullStr | Impact of Nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancer |
| title_full_unstemmed | Impact of Nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancer |
| title_short | Impact of Nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancer |
| title_sort | impact of nintedanib on tumor angiogenesis and vascular normalization in a mouse model of colorectal cancer |
| url | https://doi.org/10.1007/s12672-025-03071-4 |
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