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Updated: Aug 25, 2026

Establishing a Physiologic Human Vascularized Micro-Tumor Model for Cancer Research
Published on: September 15, 2023
Tumor vascular therapy with TNF: critical review on animal models
Timo L M ten Hagen1, Alexander M M Eggermont
1Department of Surgical Oncology, Erasmus, the Netherlands.
Abstract:
To study tumor therapeutic treatment modalities, whether from a clinical, preclinical, or fundamental point of view, the use of clinically relevant animal models is indispensable. Particularly when the treatment comprises a multitargeted approach, (e.g., both tumor cells and endothelial cells are targeted), the in vitro data will be of very limited value. Well-chosen animal models will provide conclusive data on the activity of the drug in the complex in vivo setting. Moreover, when the treatment targets the stromal compartment of the tumor rather than the tumor cells directly, insight into the mechanism of action is only possible when studied in vivo. This approach is of great importance for studies on the use of tumor necrosis factor-alpha (TNFalpha) in solid tumor therapy. Although TNFalpha has shown activity toward tumor cells in vitro directly, we and others have demonstrated that an important activity of this cytokine is directed toward the tumor vasculature. To elucidate the working mechanism of TNFalpha and to test possible treatment modalities, the animal models described here are crucial. In this chapter we will describe the use of specific animal models for efficacy studies, such as isolated limb perfusion and isolated liver perfusion in the rat.
Insights
Clinically relevant animal models are essential for studying tumor therapies, especially multitargeted treatments. These models provide crucial in vivo data on drug efficacy and mechanisms, particularly for therapies like tumor necrosis factor-alpha (TNFalpha).
Area of Science:
- Oncology
- Preclinical Research
- Pharmacology
Background:
- In vitro studies have limitations for complex tumor therapeutic treatments.
- Understanding multitargeted therapies requires in vivo validation.
- Animal models are indispensable for evaluating novel cancer treatment modalities.
Purpose of the Study:
- To highlight the importance of clinically relevant animal models in cancer research.
- To emphasize the necessity of in vivo studies for multitargeted cancer therapies.
- To detail specific animal models for evaluating tumor necrosis factor-alpha (TNFalpha) efficacy.
Main Methods:
- Utilizing clinically relevant animal models for in vivo studies.
- Employing isolated limb perfusion and isolated liver perfusion in rats.
- Investigating multitargeted therapeutic approaches in a complex biological system.
Main Results:
- In vitro data is of limited value for multitargeted cancer treatments.
- Animal models provide conclusive in vivo data on drug activity.
- In vivo studies are crucial for understanding mechanisms targeting tumor stroma and vasculature.
Conclusions:
- Well-chosen animal models are critical for assessing tumor therapeutic treatment modalities.
- The efficacy and mechanisms of agents like TNFalpha in solid tumors necessitate in vivo evaluation.
- Specific perfusion models in rats are valuable for efficacy studies in cancer therapy.

