Glioblastoma: 3D model and quantum techniques to halt progression

To create a 3D model of glioblastoma by reproducing and modifying even the tumour microenvironment to study as never before how this ferocious neoplasm, which has a survival rate of just 5% five years after diagnosis, behaves, and also to study it using quantum techniques so as to investigate every aspect and behaviour. This is the heart of the five-year Q-META project, coordinated by Giada Bianchetti, a biophysicist and researcher at the Università Cattolica del Sacro Cuore in Brescia, which has been awarded a grant from the Fondo Italiano per la Scienza (FIS3) of more than EUR 1 million in the Life Science sector.

Glioblastoma, the most widespread and aggressive brain tumour in adults, represents a major challenge in the field of oncology due to its rapid progression, resistance to treatment and poor prognosis. Indeed, this tumour is characterised by key molecular alterations that, combined with its high cellular heterogeneity and a very dynamic tumour microenvironment, constitute the major obstacle to its effective treatment.

Q-META wants to study cancer like never before. "The starting point," Bianchetti explains, "is to create an unprecedented three-dimensional model of the tumour using 3D bioprinting, a technology that allows complex cell structures to be built layer by layer in a controlled manner. We will use a human glioblastoma cell line that has been extensively characterised and used in preclinical research'. The tumour cells will be embedded in a 'bio-ink', i.e. a biocompatible material that acts as a three-dimensional support, together with other key components of the tumour microenvironment, such as tumour-associated fibroblasts, which contribute to the structure and rigidity of the tissue, and endothelial cells, which simulate the vascular component. "Through sequential bioprinting," he adds, "these different cell populations will be organised into a three-dimensional 'shell' structure, which more realistically reproduces the architecture of the tumour and its microenvironment.

This approach, for the researcher, is crucial because it makes it possible to modulate 'not only the cellular composition, but also the physical and mechanical properties of the microenvironment, such as stiffness and pressure, which are central to our study'. At a later stage of the project, there could be the introduction of cells from the immune system, in order to more comprehensively analyse the interactions between tumour compartment, stroma and immune response.

Then on these models, scientists will study all the physical stimuli, such as pressure from surrounding tissues, that result in metabolic changes in tumour cells, ultimately to understand how physical forces regulate their biological behaviour, and whether this mechanism can be exploited in a controlled manner for therapeutic purposes.