From tumour perfusion to drug delivery and clinical translation of in silico cancer models.

In silico cancer models have demonstrated great potential as a tool to improve drug design, optimise the delivery of drugs to target sites in the host tissue and, hence, improve therapeutic efficacy and patient outcome. However, there are significant barriers to the successful translation of in silico technology from bench to bedside. More precisely, the specification of unknown model parameters, the necessity for models to adequately reflect in vivo conditions, and the limited amount of pertinent validation data to evaluate models' accuracy and assess their reliability, pose major obstacles in the path towards their clinical translation. This review aims to capture the state-of-the-art in in silico cancer modelling of vascularised solid tumour growth, and identify the important advances and barriers to success of these models in clinical oncology. Particular emphasis has been put on continuum-based models of cancer since they - amongst the class of mechanistic spatio-temporal modelling approaches - are well-established in simulating transport phenomena and the biomechanics of tissues, and have demonstrated potential for clinical translation. Three important avenues in in silico modelling are considered in this contribution: first, since systemic therapy is a major cancer treatment approach, we start with an overview of the tumour perfusion and angiogenesis in silico models. Next, we present the state-of-the-art in silico work encompassing the delivery of chemotherapeutic agents to cancer nanomedicines through the bloodstream, and then review continuum-based modelling approaches that demonstrate great promise for successful clinical translation. We conclude with a discussion of what we view to be the key challenges and opportunities for in silico modelling in personalised and precision medicine.