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Human Neuroendocrine Tumor Cell Lines as a Three-Dimensional Model for the Study of Human Neuroendocrine Tumor Therapy
Published on: August 14, 2012
A study of pipeline drugs in neuroendocrine tumors
Catherine T Anthony1, Juan G Bastidas, Jessica L Thomson
1Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. cantho@lsuhsc.edu
Purpose:
Inhibition of neovessel development can stabilize tumor growth. A rapid in vitro method that can evaluate the effectiveness of anti-angiogenic drugs would aid in drug development. We tested a series of investigational agents to determine their ability to inhibit angiogenesis in our in vitro human angiogenesis model.
Methods:
A total of 74 neuroendocrine tumors were tested with five therapeutic agents for anti-angiogenic activity. Angiogenic responses were assessed visually and the percent of tumor explants that developed an angiogenic response was determined. The extent of neovessel growth was rated using a validated semi-quantitative visual scale. Analysis of variance was used to compare treatment outcome results to control values for these angiogenic parameters.
Results:
Vatalanib (2 × 10(-5) M) and patupilone (1 × 10(-8) M) were highly effective inhibitors of human tumor angiogenesis (mean overall angiogenic response for drug versus control 1.3 vs. 5.9 and 0.2 vs. 5.2, respectively) and were statistically significant at p <0.0001. Imatinib (2.5 × 10(-6) M) and everolimus (1 × 10(-8) M) were also effective (mean overall angiogenic response for drug versus control 2.2 vs. 5.9 and 4.5 vs. 5.9, respectively), and these were also statistically significant at p <0.0001. Pasireotide (1 × 10(-8) M) had no effect on angiogenesis (mean overall angiogenic response for drug vs. control 5.5 vs. 5.2).
Conclusions:
Significant differences in angiogenic response to test drugs were noted in this neuroendocrine patient population. In vitro screening of a large series of fresh human tumors may be a cost-effective way to select drugs for continued clinical development.
Insights
This study evaluated anti-angiogenic drugs in a human tumor model. Vatalanib, patupilone, imatinib, and everolimus effectively inhibited tumor angiogenesis, while pasireotide showed no effect.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Tumor growth relies on new blood vessel development (angiogenesis).
- Inhibiting angiogenesis is a strategy to stabilize tumors.
- A rapid in vitro method is needed to assess anti-angiogenic drug efficacy.
Purpose of the Study:
- To evaluate the anti-angiogenic potential of investigational agents using an in vitro human angiogenesis model.
- To identify effective drugs for inhibiting tumor angiogenesis in neuroendocrine tumors.
Main Methods:
- Tested 74 neuroendocrine tumors against five therapeutic agents.
- Assessed angiogenic responses visually and quantified neovessel growth.
- Used a validated semi-quantitative scale and analysis of variance for statistical comparison.
Main Results:
- Vatalanib and patupilone significantly inhibited human tumor angiogenesis (p <0.0001).
- Imatinib and everolimus also demonstrated significant anti-angiogenic effects (p <0.0001).
- Pasireotide did not affect angiogenesis in this model.
Conclusions:
- Significant variations in drug-induced angiogenic response were observed in neuroendocrine tumors.
- In vitro screening of human tumors offers a cost-effective approach for selecting drugs for clinical development.