Breast cancer remains one of the leading causes of cancer mortality among women. The main causes of death are related to recurrence and metastasis. One major limitation in breast cancer research field is that there are few in vitro models of breast cancer able to predict clinical patient’s outcome. The main reason of this failure is that the present models do not take account for complexity or heterogeneity. Therefore, innovative models are now required to better represent tumor fidelity. Organoids are miniature forms of tissues that exhibit three-dimensional architecture and able to maintain phenotypical properties. Organoids mimic physiological features of organs and at the same time can be cultured in a dish. Therefore, they could be used as model for disease, including cancer. Thanks to their capacity to grow in three dimensions, cancer organoids can recapitulate the complex architecture and interaction among cells and thus may mimic patient behaviour. Advances in generating and characterizing simple and complex (with added stromal components) three-dimensional in vitro models may be crucial for studying drug response and for personalized treatment of cancer, in particular for breast cancer.
BARRICADE made important advances pursuing 3 objectives:
The first objective was to generate a biobank of BC patients-derived organoids and use them for developing a patient unique drug screening profile. For this purpose, Barricade set up a novel type of bioreactors based on the interaction organoids-stroma, increasing in this manner the yield of organoids production for their pre-clinical downstream use.The second objective was to assess the potentiality of organoids to be used as preclinical drug screening model. Indeed, BARRICADE testified that organoids can be adopted for the identification of new drugs such as nanoparticles. Organoids can be used for nanoparticles drug screening using normal and cancer organoids, discriminating potentially side effects. The third objective BARRICADE evaluated the possibility of using aptamer as specific delivery system for different compounds that can modulate the penetration of chemotherapeutics such as miR-340. Indeed, organoids are used as three-dimensional mass for monitoring doxorubicin penetration, representing an exciting model for monitoring drugs able to achieve the inner part of the tumor mass. My research can benefit the society because it will contribute to taking therapy to beyond state-of-art, developing personalized anticancer therapies, giving useful information for cure setting up and characterising novel molecules that can actively affect the tumor mass .