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Brain metastases: Deciphering tumor-stroma interactions in three dimensions for the rational design of nanomedicines

Project description

Innovative 3D preclinical cancer model of brain metastases

The EU-funded 3DBrainStrom project aims to establish 3D-printed models of brain metastases that include brain extracellular matrix, stroma and serum containing immune cells flowing in functional vessels. The models will better capture clinical tissue properties, signalling pathways, haemodynamics and drug responsiveness. The researchers will exploit the new models to design three therapeutic approaches to target cellular compartments involved in brain metastases: the prevention of brain metastatic colonisation using targeted nanovaccines; the inhibition of tumour–brain stroma cells crosstalk during micrometastases progression; and the selective targeting of tumour cells. The new preclinical cancer models will bridge the translational gap in cancer therapeutics.

Objective

Brain metastases represent a major therapeutic challenge. Despite significant breakthroughs in targeted therapies, survival rates of patients with brain metastases remain poor. Nowadays, discovery, development and evaluation of new therapies are performed on human cancer cells grown in 2D on rigid plastic plates followed by in vivo testing in immunodeficient mice. These experimental settings are lacking and constitute a fundamental hurdle for the translation of preclinical discoveries into clinical practice. We propose to establish 3D-printed models of brain metastases (Aim 1), which include brain extracellular matrix, stroma and serum containing immune cells flowing in functional tumor vessels. Our unique models better capture the clinical physio-mechanical tissue properties, signaling pathways, hemodynamics and drug responsiveness. Using our 3D-printed models, we aim to develop two new fronts for identifying novel clinically-relevant molecular drivers (Aim 2) followed by the development of precision nanomedicines (Aim 3). We will exploit our vast experience in anticancer nanomedicines to design three therapeutic approaches that target various cellular compartments involved in brain metastases: 1) Prevention of brain metastatic colonization using targeted nano-vaccines, which elicit antitumor immune response; 2) Intervention of tumor-brain stroma cells crosstalk when brain micrometastases establish; 3) Regression of macrometastatic disease by selectively targeting tumor cells. These approaches will materialize using our libraries of polymeric nanocarriers that selectively accumulate in tumors.
This project will result in a paradigm shift by generating new preclinical cancer models that will bridge the translational gap in cancer therapeutics. The insights and tumor-stroma-targeted nanomedicines developed here will pave the way for prediction of patient outcome, revolutionizing our perception of tumor modelling and consequently the way we prevent and treat cancer.

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Coordinator

TEL AVIV UNIVERSITY
Net EU contribution
€ 2 353 125,00
Other funding
€ 0,00

Beneficiaries (1)