Periodic Reporting for period 1 - BARRICADE (evolutionary platform to predict breast cancer (BC) patients outcome and response to therapy)
Periodo di rendicontazione: 2020-09-01 al 2022-08-31
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 .
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 .
The project set up a novel bioreactor organoids-based for preclinical screening and confirm the use of organoids as 3D model for cancer discovery and drug efficacy assessment. A novel type of bioreactors based on the interaction of stroma-organoids has been set up. Results demonstrate the possibility to use organoids, after their amplification in the BARRICADE bioreactors, as 3d model more closed to the in vivo conditions, compared to organoids grown in Matrigel, improving the potentiality of organoids to be used as preclinical in vitro model. Secondly, the organoids can be used as instrument for testing novel drug and monitoring novel compound able to actively achieved the inner core of the tumour mass, overcoming the obstacles of the three-dimensional structure. For these reasons, organoids represent an exciting preclinical model, more closed to the patient’s tumor in vivo.
Exploitation and Dissemination overview:
These results have been shown during meetings and events (like seminars and monthly meetings).
The following scientific articles have been published or submitted by Dr Roscigno during the MSCA individual fellowship on open access journals and public repositories (Zenodo), with acknowledgment to the EU Horizon 2020 funding:
- Four research articles and one review have been published from September 2020 by Dr Roscigno (impact factors range: 6.11-27.20 with 19 total citations)
Exploitation and Dissemination overview:
These results have been shown during meetings and events (like seminars and monthly meetings).
The following scientific articles have been published or submitted by Dr Roscigno during the MSCA individual fellowship on open access journals and public repositories (Zenodo), with acknowledgment to the EU Horizon 2020 funding:
- Four research articles and one review have been published from September 2020 by Dr Roscigno (impact factors range: 6.11-27.20 with 19 total citations)
Although organoids are now widely used, they are also under-investigated and often poorly validated as preclinical model. Indeed, the influence of the matrix is not currently understood and this can have a great impact on cellular pathways and tumour behaviour. For this reason, BARRICADE represents an important contribution to the state of the art setting up a novel type of bioreactor based on fibroblasts/stroma interaction, demonstrating the importance of the tumour microenvironment for a correct organoids growth and longer propagation. For this reason, my research has a great socio-economic impact because the organoids can be used for predicting in vitro tumour response before patient undergoes to blind therapy. In this manner, the therapeutic approach of each patient can be set up during its management in a personalized form, avoiding gaps, useless toxicities and a losing of time useful for patient’s cure. Furthermore, BARRICADE will help to characterize new molecules able to penetrate in the 3d structure overcoming physical barriers differently to the 2D system.