Mouse Cancer Models for Integrated Tissue/Serum Proteomics and Molecular Imaging

Stanford University, Stanford CA

Investigators

Linked publications & trials

Abstract

Nanotechnology has the potential to significantly impact the development of small animal models of cancer[unreadable] including models to test new antineoplastic therapies. In this project we will develop mouse tumor xenoqraft[unreadable] models that will allow us to test if we can combine both tissue/serum nanosensor based proteomic analysis[unreadable] and molecular imaging with targeted fluorescent quantum dots to predict and monitor treatment response[unreadable] with specific therapies. These models are important to the overall vision of this CCNE-TR for which would[unreadable] like to eventually utilize ex vivo nanosensors and in vivo molecular imaging in cancer patients for improving[unreadable] how we predict and monitor response to therapies. In Aim 1 we will optimize small animal optical imaging[unreadable] instrumentation for imaging quantum dots and also work with General Electric Global Research to develop[unreadable] and test a new frequency domain optical imaging instrument. In Aim 2 we will utilize biologically targeted[unreadable] quantum dots developed in Projects 5 and 6 to image tumors in living mice. We will proceed systematically[unreadable] from targeting one known tumor cell surface antigen (CD20 in our lymphoma xenograft model) to targeting[unreadable] several known tumor cell surface antigens (her2/her3/PSCA in our prostate cancer model), before expanding[unreadable] our target range to neovascularization (avp3 Integrin) and extracellular matrix targets (Matrix[unreadable] metalloproteinase 2, MMP2). In Aim 3 we will develop mouse models of lymphoma for testing antineoplastic[unreadable] therapies in order to study changes in proteins at the cell membrane, in the secretome, and in serum. Cell[unreadable] surface and serum proteome will be analyzed by Solid Phase Extraction of Glycoproteins (SPEC) and Liquid[unreadable] Chromatography Mass Spectrometry (SPEG/MS), whereas secretome will be assessed by biotin capture[unreadable] and subsequent cellular functional profiling array for changes that are predictive of response to therapy. We[unreadable] will test two lymphoma therapy models, one xenograft model for human lymphoma mimicking response vs.[unreadable] resistance to Rituxan therapy, and a mouse pre-clinical model of response vs. resistance to targeted[unreadable] inactivation of the MYC oncogene. In Aim 4 we will test a mouse cancer model using the results from the[unreadable] previous three aims in order to determine the utility of integrating ex vivo and in vivo nanotechnologies to[unreadable] determine protein changes in the tissue/serum and to image molecular changes pre and post-therapy. The[unreadable] significance of this work is that it should help set the foundation for using ex vivo nanosensors in clinical[unreadable] trials, to allow development of novel molecular imaging probes for clinical trials, and to improve drug testing[unreadable] in small animal cancer models. This should lead to marked improvement in predicting and monitoring[unreadable] response to therapy in cancer patients.