Advanced Nanosystems for a New Era in Molecular Oncology - NEWTON

NEWTON is an interdisciplinary national consortium, coordinated by the School of Medicine at the University of Torino, aimed to exploit 3D tumor models connected with innovative technologies designed to improve sensitivity and specificity of biomarker assays. These models are better platforms for validating the mechanisms and the efficacy of novel therapeutic strategies arising from the new targets identified by Newton proteomic, miRnomic and transcriptomic analyses. Moreover, they can be used to provide improved testing of new drugs. The final aim is the miniaturization of the optimized in vitro 3D models into 3D Lab-on a-Chip (3D-LOC) permitting much higher throughput testing of drugs and biomarkers.

Main role of FBK was the development of smart biointerfaces for the specific capture of circulating biomarkers; the most suitable biosurfaces were included in microdevices for the capture, concentration and detection of such biomarkers.

Project started on 22th February 2012, ended on 22th February 2017

Project funded by MIUR (Italian Ministry for Education, University and Research, protocol number: RBAP11BYNP) grants-FIRB 2012-2016 for public/private structures involved in research fields characterized by strategic value.

Tumors are three dimensional (3D) structures, immersed in a dynamic networking both at genetic and protein level. Our ability to understand their formation, function, and pathology has often depended on two-dimensional (2D) cell culture studies or on animal model systems. Cells grown on flat 2D tissue culture substrates can differ considerably in their morphology, cell-cell and cell-matrix interactions, and differentiation from those growing in more physiological 3D environments. At the other end animal models frequently provide definitive tests of the importance of specific molecules and processes, but they do not adequately reproduce features of, for example, human tumors, drug therapeutic response sand stem cell differentiation. In vitro 3D tissue models provide a third approach that bridges the gap between traditional cell culture and animal models. On these bases, the final goal of NEWTON is to face the following unsolved problems in oncology : i) the feature of the dynamic networking within mutated oncogenes, which enables activation of metastatic phenotype; ii) the modulatory effect of microenvironment; iii) the characterization of cancer stem cells and their role in cancer onset: iv) the genetic heterogeneity of tumor mass and v) the poor patients’ stratification based on the genetic, transcriptomic and proteomic features of the tumor.

To reach its aim NEWTON is organized in three integrated platforms. The in vitro platform will set up the 3D models and collaborate with the technological platform to build a 3D Lab-on-a-Chip. The in vivo platform will organize mirrored experiments in mice to provide data for comparison. Finally the technological platform will provide: 1) new technologies to increase sensitivity and specificity of bioassay based on Micro Electro-Mechanical System and photonic crystals; 2) micro-scaffold for 3D models, with capability to tune physical, chemical and mechanical properties as well as to tailor bioactive characteristics by introduction of matricellular cues, or more in general, bioactive moieties; 3) the integration of the technological devices to produce a 3D-LOC.

Major advances from NEWTON include: 1) robust assays, available to all, for improved drug testing 2) the ability to test, specifically, novel therapies that target stromal cells and mimic metabolic parameters (pO2, pH), 3) cross-validation of the “omics” data derived from the original tumor and in vitro and in vivo models derived from the same tumor, 4) combining our “omics” data with other datasets and with the clinical outcome represent a powerful tool to identify “omic” signatures of responder and non-responder patients; 5) fabrication of technological devices.

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