In-silico dynamic analysis of cytotoxic drug administration to solid tumours: Effect of binding affinity and vessel permeability

摘要

Author summary One of the main challenges in optimising cancer therapy is understanding the in-vivo cancer environment and how it changes over time. The efficacy of chemotherapeutic drugs is known to be strongly dependent on blood vessel wall properties and the architecture of the developing tumour vasculature, which in turn are dependent on biochemical and mechanical interactions between cancer cells and their microenvironment. Here we present a novel in-silico modelling framework of dynamic tumour growth, angiogenesis and drug delivery, and we use it to explore biophysical factors governing the efficient delivery of cytotoxic drugs to solid tumours. We find that the time of treatment and vessel permeability are important factors for the efficacy of chemical agents with low binding affinity, that high affinity drugs can impact the tumour vasculature remodelling and bring vascular structure back to a more normalised state, and that the combination of large-sized vessel wall pores and high affinity enhances cytotoxic drug delivery and efficacy. These results have implications for treatment planning and optimisation, and show how in-silico models can be used to help understand and optimise cancer therapy.