Systematically understanding the effects of drugs on solid tumours is very challenging as it involves the interplay between drug transport in the blood and interstitium as well as intracellular responses mediated by complex regulatory networks. Often, the effects of drugs are studied from either a transport-centric or a cell-centric viewpoint. In this talk we develop an in-silico framework and platform to investigate the interplay between transport and cellular mechanisms.

We start with a simplified tumour-cord model, incorporating drug transport in the interstitium and its effect on killing cells through multiple models of the apoptotic pathway. We carefully investigate the interplay between the drug dosage input, its transport and cellular effects.

We build on this to investigate the effect of induced drug resistance mechanisms in our in-silico framework. We investigate two induced drug resistance mechanisms, one involving enhanced pumping out of drugs through ABC-transporters, and a second mechanism which involves internal sequestration/reduction of drug concentration. The effects of each of these mechanisms is studied at the cell and tissue level. We show how these mechanisms can have contrasting effects  at the tissue level.  If time permits, we will  discuss other aspects of the interplay between drug delivery, transport and cellular factors.

This is work done with Cong Liu and Xiaoyun Xu.