Triple angiokinase inhibition, tumour hypoxia and radiation response of FaDu human squamous cell carcinomas.

Abstract

BACKGROUND AND PURPOSE:

To test the effect of BIBF 1120, a novel small molecule inhibitor of multiple angiogenic receptor tyrosine kinases, on the hypoxia and radiation response of tumours.

MATERIALS AND METHODS:

Poorly differentiated human squamous cell carcinoma FaDu growing in nude mice was treated with BIBF 1120 and investigated by functional histology. To test the effect of BIBF 1120 on the radiobiological hypoxic fraction (rHF), the number and intrinsic radiation sensitivity of tumour stem cells and the outcome after fractionated irradiation, a series of local tumour control assays were performed.

RESULTS:

BIBF 1120 significantly reduced the vessel area, vessel area with a perfusion signal and tumour growth rate but did not affect tumour hypoxia or the number and intrinsic radiation sensitivity of tumour stem cells. Concurrent BIBF 1120 had no effect on local tumour control after fractionated irradiation.

CONCLUSION:

Triple angiokinase inhibition resulted in a clear-cut decrease of angiogenesis, vessel area with a perfusion signal and tumour growth but did not change tumour hypoxia or radiation response of tumour stem cells. Further experiments into mechanisms of interaction between anti-angiogenic strategies and irradiation appear to be necessary to better define and exploit the potential of this strategy to improve local tumour control after fractionated radiotherapy.

• Authors: Daniel Zips, Katja Le, Ala Yaromina, Annegret Dörfler, Wolfgang Eicheler, Xuanjing Zhou, Peter Geyer, Frank Hilberg, Michael Baumann
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 92 Issue 3 Pg. 405-10 (Sep 2009) ISSN: 1879-0887 [Electronic] Ireland
• PMID: 19409639 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• nintedanib

Topics

• Animals
• Carcinoma, Squamous Cell (drug therapy, pathology, radiotherapy)
• Cell Hypoxia (drug effects, radiation effects)
• Cell Survival (drug effects, radiation effects)
• Disease Models, Animal
• Dose Fractionation, Radiation
• Dose-Response Relationship, Drug
• Dose-Response Relationship, Radiation
• Female
• Immunohistochemistry
• Indoles (pharmacology)
• Laryngeal Neoplasms (drug therapy, pathology, radiotherapy)
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neovascularization, Pathologic (prevention & control)
• Probability
• Radiation Tolerance (drug effects)
• Random Allocation
• Reference Values