Personalised Mechanobiological Models to Predict Tumour Growth and Anti-Cancer Drug Penetration

Personalised cancer medicine presents an exciting frontier in healthcare that tailors disease mitigation and intervention to an individual patient. However, existing technologies fail to leverage the physical forces that underpin stress-dependent tumour growth and the subsequent evolution of biomechanical resistance to anti-cancer drugs. Furthermore, the fundamental mechanisms governing such force-sensitivity have yet to be uncovered; this deficiency in scientific understanding of the active biomechanical behaviour of tumours and control of drug penetration has hindered the progression of anti-cancer therapy. In this project, an advanced computational modelling framework will first be developed to uncover the mechanisms underlying stress-dependent cell and tissue growth, coupling the thermodynamics of cellular volume control with active force generation and intracellular transport. Novel experimental analysis of 3D tumour spheroid growth and single cell biomechanics will reinforce the framework to gain a new understanding of how mechanical loading can prevent tumour cell division and the role of intracellular exchange in multi-cellular growth control. The models will then be extended to determine the role of growth-induced stress and cell compaction in restricting drug penetration, and whether this can be mitigated by promoting intracellular drug perfusion. Finally, integrated patient-derived computational and tumour organoid models will be developed for prediction of growth and emergent biomechanical resistance to anti-cancer drugs, motivating model-led mechanobiological therapy in an animal model of breast cancer. The overarching objective of this ground-breaking project is to pioneer a personalised healthcare framework for prediction of mechanically-regulated cancer and treatment outcomes, with remarkable potential to drive a paradigm shift in patient-specific diagnosis and treatment of cancer.