Abstract
According to the WHO 2020, 30% of premature deaths from non-communicable diseases are due to cancer. Most of the development of new anti-cancer drugs is done on cellular models. Studies of the modes of action of drugs and of cancer biology are done preferably on models too, in view of the reduction of costs, of experimental time, and of the use of animals in research. Cancer models are needed that can better recapitulate the complexity of human cancer and ultimately reduce the failure rate of preclinically-approved cancer drugs in clinical trials (now estimated at 97%). The tumor microenvironment (TME) is a complex milieu of different types of cells (tumor and non-tumor), extracellular matrix, and chemicals that are crucial to the development of cancer and to its response to pharmacological treatments. In vitro cell models (2D and 3D) are usually limited as they cannot generally recapitulate the complexity of the TME. Additionally, often even comparatively simple 3D cancer models are not suited to parallel, high-throughput assays as they lack the homogeneity and reproducibility necessary for automated and statistical treatment. We aim at developing a novel technological platform that synergizes custom-developed bioprinting technology with 3D cell culture in designed microwells to obtain a large number of structurally homogeneous complex 3D cancer spheroids. These will be composed of different cell types, matrix, and other optional components. The technology will allow unprecedented control of the structure of spheroids, to better recapitulate the architecture of real tumors. This advancement has not been achieved so far. The implementation and the validation of the proposed technology will be done by co-developing bioprinted models of two different high-incidence cancers: breast cancer and colorectal cancer. The produced complex 3D models will be characterized with respect to the current biological knowledge base and available clinical data and include morphological, microscopic, molecular, and genetic profiling. Testing of the pharmacological response of the models will be compared with that of simpler in vitro models and treatments. The new technology will prove useful to a large community of local and international researchers and industries interested in the role of the cancer microenvironment and in the development and screening of new drug candidates or cocktails. Ultimately, the technology should enable the production of relevant in vitro models of individual patients’ cancers to test drug response before treatment in order to maximize efficacy, reduce side effects and cancer drug resistance.
Project details
Unibo Team Leader: Dario De Biase
Unibo involved Department/s:
Dipartimento di Farmacia e Biotecnologie
Coordinator:
CNR - Consiglio Nazionale delle Ricerche(Italy)
Total Unibo Contribution: Euro (EUR) 92.553,00
Project Duration in months: 24
Start Date:
18/10/2023
End Date:
28/02/2026
