SPOKE 3
Predictive Models
Advanced predictive models for prognosis, therapeutic response, and for testing the efficacy and safety of new drugs and treatments in a rapid and personalized way.
Spoke Leader and Expertise
Università degli Studi di Palermo
The University of Palermo is recognized for its well-established expertise in cellular biology, translational research, and the development of advanced experimental models for precision medicine. Within HEAL Italia, Spoke 3 represents the bridge between understanding the biological mechanisms of disease and predicting therapeutic response, directly contributing to the personalization of treatments.
Partner
- BI-REX – Big Data Innovation & Research Excellence
- IRCCS IFO – Istituti Fisioterapici Ospitalieri
- Istituto Oncologico del Mediterraneo S.p.A.
- Istituto Superiore di Sanità
- Istituto di Ricerche Farmacologiche Mario Negri
- Sapienza Università di Roma
- SIT – Sordina IORT Technologies S.p.A.
- Università degli Studi di Roma Tor Vergata
- Alma Mater Studiorum Università di Bologna
- Università degli Studi di Cagliari
- Università degli Studi di Catania
- Università degli Studi di Foggia
- Università degli Studi di Milano-Bicocca
- Università degli Studi di Modena e Reggio Emilia
- Università di Pisa
- Università Politecnica delle Marche
Scientific Coordinator
Prof. Giorgio Stassi
Mission
The mission of the thematic network (Spoke 3) is to anticipate patients’ responses to therapies, reducing clinical uncertainty and improving treatment appropriateness. In precision medicine, understanding in advance whether a therapy will be effective makes it possible to avoid unnecessary or potentially harmful treatments.
Spoke 3 works to make this prediction possible through experimental and computational models that replicate the behavior of diseased cells and tissues.
Objectives
- Improve the ability to predict individual therapeutic response.
- Reduce treatment failure through more targeted selection.
- Support the development of new therapeutic strategies.
- Provide predictive tools that can be used in clinical trials.
Activities
The activities of Spoke 3 focus on the creation and use of advanced predictive models that simulate biological responses to drugs, radiation, and innovative therapies. A key element is the development of organoids—three-dimensional structures grown in the laboratory from patient-derived cells—that faithfully reproduce the characteristics of the original tissue.
Alongside organoids, the Spoke develops cellular and animal models to study mechanisms of treatment resistance and to identify new therapeutic targets. The activities also include the design of computational models that integrate biological and clinical data, enabling the simulation of therapeutic scenarios and the prediction of disease progression over time.
A further area of activity concerns the study of biomechanical and metabolic factors that influence the behavior of tumor cells and their response to therapies.
Areas of work
Integration of experimental and computational models for human 3D cell cultures characterized by specific genetic mutations or alterations in RNA/protein biogenesis.
- 3D simulation of spheroidal structures using Machine Learning
- Molecular circuits regulating 3D cell growth in physio-pathological phenotypes
Simulation of mutated proteins and complex structures using Quantum Computing and AI
- Quantum computing techniques applied to biochemical systems, molecular biology, and organic chemistry
- Integrated in silico evaluation of the impact of mutations on protein structure, function, and interactions
Dynamic pharmacophore docking simulations of molecules with genetic alterations
- Computational optimization of molecular binding and docking affinity
- Molecular synthesis for the experimental validation of computational models
- Early diagnostics: translation of tools from the laboratory to the clinic (Bench to Bedside)
Preclinical models for precision prevention, therapy, and diagnostics
- 3D modeling of spheroidal structures for estimating the risk of disease onset and progression
- Development of in vitro models for response to radiotherapy and local hyperthermia (HT)
- Experimental validation at single-cell resolution (single-cell level)
- Generation and optimization of preclinical animal models based on the use of organoids
- Murine models for the study of mitochondrial metabolism
- Innovative systems for FLASH electron radiotherapy: from in silico modeling to preclinical validation in animal models and organoids for deep tumors
Projects Funded through Cascade Calls
MECHANOMET
Tracing, studying, and disabling and cross talk between mechanotransduction, cancer cells, and CAFs in the metastatic breast cancer tumor microenvironment
The project aims to decipher the influence of the biomechanical properties of the extracellular matrix on the biology of metastatic cells and tumor-associated fibroblasts, integrating organotypic systems and transgenic murine models of breast cancer to test the functional impact of mechanotransduction in preclinical settings. Through the use of synthetic biology and the development of new high-resolution cellular imaging tools, the research will reconstruct the dynamic interactions between diseased cells and the host microenvironment, providing an advanced platform for characterizing innovative pharmacological compounds. The ultimate goal is to identify targets capable of modulating matrix remodeling and overcoming resistance to conventional treatments, establishing new therapeutic strategies to effectively prevent metastatic relapse by acting on the physical and molecular foundations of tumor progression.
PLANNING
A PLAtform to ideNtify aNd characterIze mitochoNdrial druGs
The project is aimed at developing a pipeline of innovative mitochondrial-targeted drugs, named Opanibs, Micanibs, Mikatibs, and Precinibs, designed to selectively target key molecular components such as the Opa1 protein, the mitochondrial calcium uniporter ($Ca^{2+}$), the mitochondrial $K_{ATP}$ channel, and the P2 receptor. Through the modulation of these specific signaling pathways, the research seeks to provide advanced therapeutic solutions to counteract cancer, neurodegenerative diseases, and inflammation, transforming the regulation of mitochondrial functions into an effective clinical strategy to restore cellular homeostasis across various pathological conditions.
