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Spatiotemporal regulation of metastatic breast cancer cell fate

Project description

Understanding the dynamics of breast cancer metastasis

Metastasis is the spread of cancer cells from a primary tumour to distant organs and is responsible for most cancer-related deaths. In breast cancer, prognosis is often good before dissemination, but survival drops sharply once metastasis occurs. Therefore, it is central to understand the underlying mechanisms of metastasis for novel targeted therapies. The working hypothesis of the ERC-funded METspread project is that metastatic cells in different organs develop distinct molecular and functional traits and can drive further spread through secondary seeding. Researchers will employ advanced in vivo models and niche-labelling strategies to map metastatic behaviour across space and time. The aim is to uncover niche-specific interactions and reveal how local environments shape disease progression.

Objective

Breast cancer is the most common malignancy in women with globally over 600’000 deaths per year. While cancer diagnosis before metastasis is often associated with a favourable prognosis, due to surgical and new therapeutic approaches, once metastasis is initiated, the survival rates decline significantly. However, the understanding of this last and most detrimental phase of cancer remains at a low resolution, reflected by the lack of metastasis-targeted therapeutic options.
In fact, most of the studies have focused on the understanding of primary tumour states and their relationship to metastasis. Recently, it has emerged, however, that secondary seeding from metastatic deposits to new sites plays a role in cancer spread. We made an unexpected discovery that the cancer cells metastasised to different sites display dramatically distinct molecular and functional properties, thereby having diverse impacts on cancer progression. This highlights a previously underappreciated role of secondary seeding and emphasises the need to study metastasis at a higher resolution.
Indeed, metastasis is an evolutionary process that occurs across various organs and timescales, yet its spatiotemporal progression is a black box. To this end, we will use cutting-edge technologies such as evolving barcodes and niche-labelling systems and state-of-the-art in vivo models to identify 1) different spatiotemporally controlled metastatic behaviours, together with 2) the associated alterations in the metastatic niche and 3) specific niche-cancer crosstalk that guides the cancer expansion and metastatic properties.
This project will create a first spatiotemporal cellular model of metastasis, which will reveal how the metastatic behaviour at different sites is shaped during metastatic progression. Our research has a long-term ambition to design new therapeutic approaches informed by the metastatic profile and temporal biomarkers in patients.

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HORIZON-ERC - HORIZON ERC Grants

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(opens in new window) ERC-2025-STG

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Host institution

UNIVERSITAT BASEL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 028 936,00
Address
PETERSPLATZ 1
4051 Basel
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 028 936,00

Beneficiaries (1)

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