Modelling barriers to drug delivery and response to therapy in solid tumours using non-invasive magnetic resonance imaging (360G-Wellcome-100247_Z_12_Z)

During the growth of a tumour, high rates of cell proliferation lead to hypoxia and the upregulation of pro-angiogenic pathways. This results in a chaotic and disorganised vascular network that is typically poorly perfused, with highly permeable walls. Excessive fluid leakage through vessel walls leads to high interstitial fluid pressure (IFP) in most tumours which, alongside poor vascular perfusion, can impact significantly on drug delivery and on drug retention within the interstitium. It has long been acknowledged that putative anti-cancer drug therapies can fail in clinical trials due to poor penetration of the drug into tumour tissue. Consequently, this project aims to develop novel, non-invasive magnetic resonance imaging (MRI) techniques to measure the principle physiological parameters associated with the delivery of drugs into tumours, namely: IFP, blood flow, vascular permeability and cell density. These will be unified within a fluid mechanical model, and used as a basis for predicting the distribution of therapeutic molecules and the assessment of response to therapy, on an individual tumour basis. In the clinic, prediction of drug delivery would offer unprecedented opportunities to stratify therapeutic interventions, thereby improving patient care and enabling financial savings by avoiding ineffective and costly drug therapies, which is in accordance with the current drive for personalised medicine in oncology. Fluid dynamics in the tumour microenvironment a re complex and multi-factorial, and this project will combine novel biomedical imaging, sophisticated computational analysis and numerical simulation.