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Building a reproducible single-cell experimental workflow to capture tumour cell persistence

Project description

The biology of drug resistance in cancer

Achieving a cure in many types of cancer is hampered by the emergence of drug resistance. Before proceeding with smarter therapeutic strategies, we need to better understand residual disease after treatment and how drug-tolerant cells emerge and persist. To address these issues, the EU-funded PERSIST-SEQ project proposes to study the biology of therapeutic resistance in cancer at the single cell level. Using patient-derived organoids, mouse models and modelling techniques, researchers will profile individual cells and obtain fundamental knowledge on drug resistance in cancer. Results are expected to improve treatment decisions and patient clinical outcomes.

Objective

It is the ambition of PRESIST-SEQ to provide a new gold standard in single-cell experimental workflows the cancer research community by developing best practices, standard operating procedures (SOPs), and high-quality FAIR data, with the ultimate aim to empower them to unravel therapeutic resistance. Such, that the community can identify urgently needed markers to predict, prevent, and target tumour resistance. Cancer takes 9.6 million lives each year, 90% of which result from untreatable metastatic relapse occurring after initially (seemingly) effective treatment. Therapeutic resistance is hence a primary cause of cancer death that clinically cannot be predicted, prevented, or treated. Addressing the urgent need for smarter therapeutic strategies is however held back by the lack of standardised experimental approaches that enable studying the biology of residual disease and drug tolerant persister cells in full detail. This need encompasses best practices for single-cell sequencing, advanced modelling techniques using patient-derived organoids and xenografts, and data FAIRification for integrated experiments. To address this need, PERSIST-SEQ brings together globally leading groups in single-cell sequencing technologies, cancer modelling and therapeutic resistance. Furthermore, the consortium has a broad range of clinical samples, cell lines, 3D models (PDX and PDOs) and mice models (GEMMs) at its disposal that can be leveraged to answer a broad range of emerging questions. This positions the consortium excellently to (1) design and standardise single-cell experimental approach to study the biology of therapeutic resistance and (2) initiate the largest single-cell profiling initiative on therapeutic resistance. Importantly, PERSIST-SEQ is organised such that it can quickly adapt to emerging insights and techniques during the project, and that ensures the capture of learnings in manners that stimulate replication of workflows elsewhere.

Coordinator

STICHTING ONCODE INSTITUTE
Net EU contribution
€ 406 875,00
Address
JAARBEURSPLEIN 6
3521 AL Utrecht
Netherlands

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Region
West-Nederland Utrecht Utrecht
Activity type
Other
Links
Total cost
€ 2 156 750,00

Participants (16)