Summary
It is now widely recognized that within a tumor, not all cancer cells are alike and different tumor states (TS) exist. This process is known as tumor heterogeneity. Some cancer cells actively proliferate, while others differentiate, migrate and give rise to metastasis, or enter in a dormant state and resist to chemotherapy. The identification of distinct TS and the mechanisms that regulate their identities and functions is critical for our understanding of tumor heterogeneity. The different TS can acquire distinct phenotypes responsible for tumor progression, metastasis, and therapy resistance. In this project, using multidisciplinary approaches that combine single-cell lineage tracing, single-cell genomics, epigenomics and transcriptomics together with pharmacological treatment and genetic perturbations, we will define in a comprehensive and integrated manner the identities and functions of distinct TS at single-cell resolution in squamous cell carcinoma (SCC). Then, we will develop new genetically engineered tumor models expressing different fluorescent proteins to visualize the dynamics of TS in real time in vivo using intravital microscopy. Moreover, we will assess the roles of the identified TS by lineage ablation and identify the intrinsic and extrinsic mechanisms that regulate their transitions and functions, which will help to define new tumor vulnerabilities and provide new therapeutic opportunities.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/885093 |
| Start date: | 01-11-2020 |
| End date: | 31-10-2025 |
| Total budget - Public funding: | 2 500 000,00 Euro - 2 500 000,00 Euro |
Cordis data
Original description
It is now widely recognized that within a tumor, not all cancer cells are alike and different tumor states (TS) exist. This process is known as tumor heterogeneity. Some cancer cells actively proliferate, while others differentiate, migrate and give rise to metastasis, or enter in a dormant state and resist to chemotherapy. The identification of distinct TS and the mechanisms that regulate their identities and functions is critical for our understanding of tumor heterogeneity. The different TS can acquire distinct phenotypes responsible for tumor progression, metastasis, and therapy resistance. In this project, using multidisciplinary approaches that combine single-cell lineage tracing, single-cell genomics, epigenomics and transcriptomics together with pharmacological treatment and genetic perturbations, we will define in a comprehensive and integrated manner the identities and functions of distinct TS at single-cell resolution in squamous cell carcinoma (SCC). Then, we will develop new genetically engineered tumor models expressing different fluorescent proteins to visualize the dynamics of TS in real time in vivo using intravital microscopy. Moreover, we will assess the roles of the identified TS by lineage ablation and identify the intrinsic and extrinsic mechanisms that regulate their transitions and functions, which will help to define new tumor vulnerabilities and provide new therapeutic opportunities.Status
SIGNEDCall topic
ERC-2019-ADGUpdate Date
27-04-2024
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