Project description
Unravelling tumour complexity for better CRC treatment
Treating advanced colorectal cancer (CRC) is challenging due to therapy resistance and tumour relapse. One reason is the tumour’s ability to maintain diverse cancer cell populations, each specialised in growth, invasion, or survival. Cancer cells can also change their state, allowing even a single surviving cell to regenerate a full tumour. Supported by the Marie Skłodowska-Curie Actions programme, the SelfOrg project investigates how tumours develop this complexity. While external signals are known to influence tumour plasticity, SelfOrg explores the role of cancer cells’ intrinsic ability to self-organise. Using bioengineered human organoids, mouse tumour models, and patient-derived organoid biobanks, researchers aim to uncover new mechanisms behind CRC progression. This novel approach could lead to better treatments and improved patient survival.
Objective
Colorectal cancer (CRC) remains a major health challenge, with a survival rate of 15% in stage IV cases due to therapy resistance and tumor relapse. A key barrier to effective treatment is the high degree of intratumor heterogeneity and plasticity. These features enable the coexistance of diverse cancer cell populations within a tumor, each of them specialized in key functions such as proliferation, invasion or resistance to treatment. Additionally, phenotypic plasticity grant these cancer cells flexibility to dynamically tune their phenotype, to the extent that a single surviving cell can regenerate a full heterogeneous tumor. Despite their crucial role in CRC pathology, the biological mechanisms driving tumor heterogeneity and plasticity remain poorly understood.
Current research suggests that tumor plasticity is driven by microenvironmental cues, where external signals induce specific cell states within localized tumor niches. However, my preliminary data reveal that cancer cells possess an intrinsic ability to self-organize and establish heterogeneity even in the absence of external signals. SelfOrg will tackle the unexplored contribution of self-organization to tumor heterogeneity and plasticity. To do so, I will combine quantitative measurements in bioengineered human organoids with physiologically relevant mouse tumor models to dissect the intrinsic mechanochemical signals regulating tumor heterogeneity. A systematic, image-based analysis of a patient-derived organoid (PDO) biobank will further assess the clinical implications of self-organization for patient prognosis.
By leveraging my expertise in organoid mechanobiology and the host lab's proficiency in PDOs and translational cancer research, SelfOrg is uniquely positioned to address the problem of tumor heterogeneity from the novel perspective of self-organization. This innovative approach has the potential to uncover new therapeutic targets to improve survival and quality of life for CRC patients.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine pathology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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08908 L'Hospitalet De Llobregat
Spain
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