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A Study of Pipeline Drugs in Neuroendocrine Tumors

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Abstract

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.

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Acknowledgments

We are grateful to Novartis for the donation of the drugs used in this study. Special recognition is given to all the residents and staff of the departments of Surgery and Pathology at Louisiana State University Health Sciences Center in New Orleans for helping in collecting and processing the specimens.

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Authors and Affiliations

  1. Department of Surgery, Louisiana State University Health Sciences Center, 533 Bolivar Street, Room 720, New Orleans, LA, 70112, USA

    Catherine T. Anthony, Juan G. Bastidas, John Lyons III, James M. Lewis, Joshua E. Schwimer, Peter Casey, Jennifer Abadie, Daniel J. Frey, Yi-Zarn Wang, J. Philip Boudreaux & Eugene A. Woltering

  2. USDA ARS Southern Regional Research Center, Baton Rouge, LA, USA

    Jessica L. Thomson

  3. 200 West Esplanade Ave. Suite 200, Kenner, LA, 70065, USA

    Eugene A. Woltering

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  1. Catherine T. Anthony
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  2. Juan G. Bastidas
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  3. Jessica L. Thomson
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  4. John Lyons III
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  5. James M. Lewis
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  6. Joshua E. Schwimer
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  12. Eugene A. Woltering
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Correspondence to Catherine T. Anthony.

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Anthony, C.T., Bastidas, J.G., Thomson, J.L. et al. A Study of Pipeline Drugs in Neuroendocrine Tumors. J Gastrointest Canc 43, 296–304 (2012). https://doi.org/10.1007/s12029-011-9286-9

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