Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Multidisciplinary Hyper-Modeling Scheme in Personalized In Silico Oncology: Coupling Cell Kinetics With Metabolism, Signaling Networks and Biomechanics As Plug-In Component Models of a Cancer Digital Twin

Version 1 : Received: 7 March 2024 / Approved: 8 March 2024 / Online: 8 March 2024 (04:11:35 CET)

How to cite: Kolokotroni, E.; Abler, D.; Ghosh, A.; Tzamali, E.; Grogan, J.; Georgiadi, E.; Büchler, P.; Radhakrishnan, R.; Byrne, H.; Sakkalis, V.; Nikiforaki, K.; Karatzanis, I.; McFarlane, N.J.; Kaba, D.; Dong, F.; Bohle, R.M.; Meese, E.; Graf, N.; Stamatakos, G. A Multidisciplinary Hyper-Modeling Scheme in Personalized In Silico Oncology: Coupling Cell Kinetics With Metabolism, Signaling Networks and Biomechanics As Plug-In Component Models of a Cancer Digital Twin. Preprints 2024, 2024030490. https://doi.org/10.20944/preprints202403.0490.v1 Kolokotroni, E.; Abler, D.; Ghosh, A.; Tzamali, E.; Grogan, J.; Georgiadi, E.; Büchler, P.; Radhakrishnan, R.; Byrne, H.; Sakkalis, V.; Nikiforaki, K.; Karatzanis, I.; McFarlane, N.J.; Kaba, D.; Dong, F.; Bohle, R.M.; Meese, E.; Graf, N.; Stamatakos, G. A Multidisciplinary Hyper-Modeling Scheme in Personalized In Silico Oncology: Coupling Cell Kinetics With Metabolism, Signaling Networks and Biomechanics As Plug-In Component Models of a Cancer Digital Twin. Preprints 2024, 2024030490. https://doi.org/10.20944/preprints202403.0490.v1

Abstract

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

Keywords

in silico medicine; in silico oncology; cancer; hypermodeling; digital twin; virtual twin; computational oncology; Wilms tumor; non small cell lung cancer

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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