A main goal of mathematical and computational oncology is to develop quantitative tools to determine the most effective therapies for each individual patient. This involves predicting the right drug to be administered at the right time and at the right dose. Such an approach is known as precision medicine. Mathematical modelling can play an invaluable role in the development of such therapeutic strategies, since it allows for relatively fast, efficient and inexpensive simulations of a large number of treatment schedules in order to find the most effective. This review is a survey of mathematical models that explicitly take into account the spatial architecture of three-dimensional tumours and address tumour development, progression and response to treatments. In particular, we discuss models of epithelial acini, multicellular spheroids, normal and tumour spheroids and organoids, and multi-component tissues. Our intent is to showcase how these in silico models can be applied to patient-specific data to assess which therapeutic strategies will be the most efficient. We also present the concept of virtual clinical trials that integrate standard-of-care patient data, medical imaging, organ-on-chip experiments and computational models to determine personalized medical treatment strategies.

Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

Tumors are complex multicellular heterogeneous systems comprised of components that interact with and modify one another. Tumor development depends on multiple factors: intrinsic, such as genetic mutations, altered signaling pathways, or variable receptor expression; and extrinsic, such as differences in nutrient supply, crosstalk with stromal or immune cells, or variable composition of the surrounding extracellular matrix. Tumors are also characterized by high cellular heterogeneity and dynamically changing tumor microenvironments. The complexity increases when this multiscale, multicomponent system is perturbed by anticancer treatments. Modeling such complex systems and predicting how tumors will respond to therapies require mathematical models that can handle various types of information and combine diverse theoretical methods on multiple temporal and spatial scales, that is, hybrid models. In this update, we discuss the progress that has been achieved during the last 10 years in the area of the hybrid modeling of tumors. The classical definition of hybrid models refers to the coupling of discrete descriptions of cells with continuous descriptions of microenvironmental factors. To reflect on the direction that the modeling field has taken, we propose extending the definition of hybrid models to include of coupling two or more different mathematical frameworks. Thus, in addition to discussing recent advances in discrete/continuous modeling, we also discuss how these two mathematical descriptions can be coupled with theoretical frameworks of optimal control, optimization, fluid dynamics, game theory, and machine learning. All these methods will be illustrated with applications to tumor development and various anticancer treatments.This article is characterized under: Analytical and Computational Methods > Computational Methods Translational, Genomic, and Systems Medicine > Therapeutic Methods Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models