Abstract A1: Onco Vasculomics (TM): A 3D tumor micro-vascular environment assessment methodology for quantifying mechanism of efficacy and toxicity of discovery-stage anti-cancer compounds.
Authors: Brauner Raul A. , Kang Kongbin , Wu Yanchun , Naumov George N. , Heymach John 
Published: August 2014

Pre-clinical evaluation of anti-tumor efficacy and toxicity profile of a compound are key components of drug development. Independent of an indication, even minute changes in the tumor vasculature can signal substantial efficacy response. Similarly, some toxicity profiles are based on vascular effects. Conventional methods for evaluating vascular changes do not capture critical 3-D properties on a population basis. Such parameters are critical for understanding the biological effects of agents targeting the tumor vasculature and/or causing vascular-associated toxicity. To address this critical unmet need, Bio-Tree developed a novel system platform which enables high-resolution 3-D, structural microvascular pattern analysis and biomarker mining in support of preclinical and translational oncology discovery space. The OncoVasculomics™ platform captures, reconstructs, and then automatically and quantitatively analyzes microvascular structures and patterns indicative of pharmacological or toxicological responses.

Methods: The effect of bevacizumab and sunitinib, were assessed using OncoVasculomics™ platform in H1975 human NSCLC and Colo205 xenograft models, respectively. The vasopressor activity of epihedrine/caffeine mixture was assessed as an example of a kidney toxicity model. Mice were systemically perfused, the tissue was macerated and the resulting vascular tumor and kidney casts were imaged and reconstructed using proprietary software. OncoVasculomics™ vascular mining software was used to derive various vascular morphology parameters.

Results: Mean tumor sizes did not significantly differ between the Bevacizumab, Sunitinib or vehicle treatment groups at the end of the experiment. Bevacizumab and sunitinib treatments resulted in 48% and 30% decrease in total tumor MVD, respectively. Bevacizumab treatment resulted in 94 % increase in “cold spot” or low vascular density regions generation and in 63% increase in “cold spot” generation. Microvascular “hot spot” generation was decreased by 49% by bevacizumab and 47% by sunitinib. Treatment with the ephedrine/caffeine mixture resulted in mousedependent toxicity profile demonstrating clear vasopression in the mouse kidneys. These studies demonstrate that a comprehensive 3D OncoVasculomic™ analysis may provide important mechanistic and toxicologic insights into the vascular effects of different classes of drugs targeting the tumor and normal organ vasculature in various animal models.

Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A1.

Citation Format: Raul A. Brauner, Kongbin Kang, Yanchun Wu, George N. Naumov, John Heymach. Onco Vasculomics (TM): A 3D tumor micro-vascular environment assessment methodology for quantifying mechanism of efficacy and toxicity of discovery-stage anti-cancer compounds. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A1.