Combined anti-angiogenic and cytotoxic treatment of a solid tumour: in silico investigation of a xenograft animal model’s digital twin
Résumé
Anti-angiogenic (AA) treatments have received significant research interest due to the key role of an-giogenesis in cancer progression. AA agents can have a strong effect on cancer regression, by blockingnew vessels and reducing the density of the existing vasculature. Moreover, in a process termed vascularnormalisation, AA drugs can improve the abnormal structure and function of the tumour vasculature,enhancing the delivery of chemotherapeutics to the tumour site. Despite their promising potential, animproved understanding of AA treatments is necessary to optimise their administration as a monotherapy orin combination with other cancer treatments. In this work we present anin silicomultiscale cancer modelwhich is used to systematically interrogate the role of individual mechanisms of action of AA drugs intumour regression. Focus is placed on the reduction of vascular density and on vascular normalisation througha parametric study, which are considered either as monotherapies or in combination with conventional/metronomic chemotherapy. The model is specified to data from a mammary carcinoma xenograft in im-munodeficient mice, to enhance the physiological relevance of model predictions. Our results suggest thatconventional chemotherapy might be more beneficial when combined with AA treatments, hindering tumourgrowth without causing excessive damage on healthy tissue. Notably, metronomic chemotherapy has shownsignificant potential in stopping tumour growth with minimal toxicity, even as a monotherapy. Our findingsunderpin the potential of ourin silicoframework for non-invasive and cost-effective evaluation of treatmentstrategies, which can enhance our understanding of combined therapeutic strategies and contribute towardsimproving cancer treatment management.