Abstract

There are many promising new drugs and delivery routes in development in the fight against cancer but there remains a fundamental knowledge gap in the translation of discovery science to the clinic: the tumour biophysical microenvironment. Aggressive tumours are hallmarked by a dense, hypoxic, mechanically stiff stroma that not only accelerates disease progression, but provides a physical barrier to drug delivery. High densities of cells and extracellular matrix (ECM) proteins and high interstitial pressures block the penetration of drugs into the tumour mass, leading to long term treatment failure. Yet despite this, most pre-clinical testing is performed on models that neglect to incorporate critical biophysical features of the tumour microenvironment, including hydraulic and mechanical accuracy. Organ-on-chip is a branch of microfluidics that allows the culture of cells in devices that provides a means to mimic some of the biophysical features present in tumours in the body. This allows for a more accurate test bed for assessing new drugs. In addition, these devices provide models for investigative research into the mechanism of new delivery approaches, which is not easily achievable in vivo. I will present recent work from my group on understanding the biophysical properties of tumours using rheology and AFM in order to develop more accurate pre-clinical test beds and how we use organ-on-chip devices to assess new methods for delivering treatments, including microbubble enhanced drug delivery.