Skip to main content
Go to the home page of the European Commission (opens in new window)
English en
CORDIS - EU research results
CORDIS

Addressing the role of self-organization in tumor heterogeneity and plasticity

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)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

See all projects funded under this funding scheme

Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

See all projects funded under this call

Coordinator

FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE
Net EU contribution
€ 209 914,56
Address
AVENIDA GRAN VIA HOSPITALET 199-203
08908 L'Hospitalet De Llobregat
Spain
Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
Total cost
No data