Over the past few years, evidence has accumulated supporting the hypothesis that cancer robustness may be attributed to a small portion of the tumour mass, the cancer stem cells (CSCs). This leads us to propose a more target-oriented treatment for cancer. Our approach is geared towards the addition of Master Switch factors in the microenvironment of the CSCs that will lead to their differentiation into non-proliferative and non-malignant cells. These master switch factors are normally present in the normal stem cell niche to regulate homeostasis. Our proposal is subdivided in in vitro studies, in silico modelling and in vivo testing (transplantation in animal models) of stem cells representing two types of solid tumours: brain and breast cancers. To achiev e our goal, the master switch factors will be identified and delivered locally, in and around the tumour. For that purpose, we will use microbeads loaded with the Master Switch protein(s) to deliver, only locally, a high concentration of the differentiatin g factor(s), recreating a normal microenvironment. Since it relies on the addition of proteins in the environment of the cancer stem cells, we will use a lab-on-chip system to cultivate and study a small number of CSCs in a controlled microenvironment. Fin ally, it is known that not all tumours even of a same type respond in the same way or at the same speed to an identical treatment. We therefore propose to develop biomathematical models of the behaviour of the CSCs based on parameters identified first in v itro and later in vivo. This biomodelisation will help generating the control board, a realistic predictive model aiming at the custom-tailoring of the tumour treatment. We will then be able to propose a conceptually novel treatment that will include an a pproach, the facilitation of CSC differentiation, an evaluation method using biopsies in combination with the lab-on-chip and detailed treatment procedures based on predictions by the control board.
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Funding SchemeSTREP - Specific Targeted Research Project
282 Bene Ataroth