TY - JOUR
T1 - A multidisciplinary hyper-modeling scheme in personalized in silico oncology
T2 - coupling cell kinetics with metabolism, signaling networks, and biomechanics as plug-in component models of a cancer digital twin
AU - Kolokotroni, Eleni
AU - Abler, Daniel
AU - Ghosh, Alokendra
AU - Tzamali, Eleftheria
AU - Grogan, James
AU - Georgiadi, Eleni
AU - Büchler, Philippe
AU - Radhakrishnan, Ravi
AU - Byrne, Helen
AU - Sakkalis, Vangelis
AU - Nikiforaki, Katerina
AU - Karatzanis, Ioannis
AU - McFarlane, Nigel J. B.
AU - Kaba, Djibril
AU - Dong, Feng
AU - Bohle, Rainer M.
AU - Meese, Eckart
AU - Graf, Norbert
AU - Stamatakos, Georgios
PY - 2024/4/29
Y1 - 2024/4/29
N2 - 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 of the actual anatomy of a patient have been conducted. The hypermodel has also been 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 as the core of future in silico trial platforms, although additional retrospective adaptation and validation are necessary.
AB - 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 of the actual anatomy of a patient have been conducted. The hypermodel has also been 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 as the core of future in silico trial platforms, although additional retrospective adaptation and validation are necessary.
KW - digital twin
KW - in silico medicine
KW - hypermodeling
KW - cancer
KW - Wilms tumor
KW - non-small cell lung cancer
KW - in silico oncology
KW - virtual twin
KW - computational oncology
U2 - 10.3390/jpm14050475
DO - 10.3390/jpm14050475
M3 - Article
VL - 14
JO - Journal of Personalized Medicine
JF - Journal of Personalized Medicine
IS - 5
M1 - 475
ER -