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Mapping Cancer Response using Organoids and Mass cytometry

Project description

Cancer patient organoids to guide treatment

Tumours are characterised by great heterogeneity which often impedes drug effectiveness. Therefore, cancer models used in drug development must reflect disease properties in order to recapitulate their drug response. The EU-funded MaCaROM project proposes to use organoids derived from breast cancer patient samples to meet this challenge. Using mass cytometry, scientists will evaluate response of heterogeneous cancer models to different FDA-approved drugs at the single-cell level. Results will provide important information on drug sensitivity and resistance, supporting treatment decisions for improved clinical outcome and increased patient survival.

Objective

Breast cancer is the most common form of cancer in women and has a very variable prognosis. Efficacy of anticancer therapies is limited by intertumor and intratumor heterogeneity. To take these into account, tumor models should recapitulate native tumor heterogeneity and should be analysed at the single-cell level. Here, we propose to take advantage of the conserved heterogeneity of breast cancer patient-derived organoids in order to analyze their response to 45 FDA-approved drugs. These responses will be mapped in a single-cell atlas of sensitivities using mass cytometry, and the use of this atlas will be assessed for the prediction of drug sensitivity in future patient tumors and to guide treatment. We plan on exploring the best hits of this screening using imaging mass cytometry to have a spatial view of the evolution of the tumor ecosystem over time after drug treatment. This should positively impact patient treatment and survival and, more broadly, could lead to the new concept of “mapping-based precision medicine”. This project will also uncover the biology of resistance to drug treatments at unprecedented resolution. The study of the different cellular populations composing breast tumors, and their interactions, will lead to a better understanding of the tumor ecosystem and to the identification of therapies targeting specific cellular populations that could trigger tumor demise.

Coordinator

UNIVERSITAT ZURICH
Net EU contribution
€ 191 149,44
Address
RAMISTRASSE 71
8006 Zurich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 191 149,44