Glioblastoma multiforme and medulloblastoma are highly heterogeneous and particularly aggressive brain tumors. Despite typically treatments (i.e surgery, chemotherapy and radiation therapy), both cancers usually recur. More recent molecular classifications of GBM and MB have highlighted the heterogeneity that exists within pathological subtypes pointing out the role of different developmental signaling pathways in cancer pathogenesis. Due to this heterogeneity, standard therapies provide poor positive outcomes. However, based on cancer similarities, all different types of tumors start from a relatively small fraction of tumor cells, that have the ability to proliferate and maintain tumor growth.
All other cells of the bulk tumor are characterized by limited proliferative capacity and a more specified lineage potential. CSC populations are also termed tumor-initiating cells, because maintains two key properties: self-renewal and differentiation. Self-renewal is defined as the ability of a parental cell to generate an identical daughter cell and a second cell of the same or different phenotype, whereas through the process of differentiation a CSC is able to give rise to the heterogeneous cell lineages that constitute the original tumor. After this initial phase of tumor growth the CSCs become quiescent. The quiescence state is the survival strategy of cancer cells responsible for the later recurrence and relapses. Therefore, new and alternative treatment approaches are necessary to reduce not only long-term toxicity of radiotherapy or chemotherapeutic agents, but also to find a newer targeted therapeutic strategy for example targeting specifically CSCs. The goal of SUMCASTEC is to isolate selectively target quiescent malignant CSCs and subsequently induce a differentiation process to sensitize them to radio- chemotherapy treatments
SUMCASTEC explores radically new approach for cancer stem cells real time isolation and neutralization. A novel micro-optofluidic lab-on-chip (LOC) platform will be developed through a joint and iterative efforts by biologists, clinicians and engineers. For the first time, a single LOC will be able to deliver ultra-wide broadband radiation to compare cell spectral signatures, image subcellular features, and hence modulate CSCs microenvironment conditions with unprecedent space and time resolution. It will be driven to isolate CSCs from heterogeneous differentiated and stem cell populations, and force CSCs differentiation, ultimately inducing sensitivity to anticancer treatments. Extensive in vitro and in vivo testing along with biophysical modelling will validate the approach and establish the proof -of-principle within the project life-time, while laying the ground work for further development of future electrosurgical tools that will be capable CSCs neutralization in tissue.
The targeted scientific breakthrough in SUMCASTEC is the world’s first micro-optofluidic lab-on-chip platform enabling successively Cancer Stem Cells isolation via electromagnetic sensing and cell spectral signature identification, nanoscale imaging of targeted cells and their selective neutralization via electromagnetic radiations.
