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

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.