Abstract B54: Location of tumor burden influences tumor and vascular architecture, necrosis, and nanoparticle delivery

The gene and protein expression profile of a metastatic lesion can vary from the primary tumor. As a result, behavior of a secondary lesion can differ in the context of drug uptake and sensitivity as compared to the parent tumor. A better understanding of phenotypic variations that arise as a result of location of disease burden may be able to shed light on why widely used subcutaneous and orthotopic preclinical models fail to predict clinical success of drug candidates evaluated in the metastatic setting. These data can be used as a guide for preclinical study design in drug discovery. Our objective was to examine metastatic lesions from a wide range of organs in order to establish patterns of microarchitecture that may influence drug biodistribution and therefore drug efficacy in vivo. We hypothesize that metastatic lesions are phenotypically unique tumors with heterogeneous microenvironments which results in variable drug delivery and therefore drug efficacy. The investigations described compare tumor and vascular architecture of an orthotopic tumor with metastatic lesions. To study this, female NCr nude mice were inoculated with Her2/neu positive human breast cancer cells (JIMT-1) transfected with a fluorescence protein (mkate). Animals were inoculated either in the mammary fat pad (o.t.) to replicate a primary tumor, or directly into the left ventricle (i.c.) to establish systemic disease. Tumor development was monitored using in vivo fluorescence imaging (IVFI). Once me...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Heterogeneity (Intratumor and Intertumoral): Poster Presentations - Proffered Abstracts Source Type: research