Glioblastoma patients today receive radiotherapy and drugs without knowing whether their tumour tissue has enough oxygen or whether the drugs actually reach the cancer cells. The tumour’s internal plumbing—its blood vessels—is chaotic, leaky, and constantly changing, yet doctors have no way to map oxygen levels or drug concentrations at the scale of individual cells. This project will build a computational model that predicts, from standard medical scans, exactly where oxygen and chemotherapy molecules travel inside a glioblastoma. The team will first develop a graph-based method to map tumour blood vessel structure from imaging data, then use physics-based calculations to infer oxygen and drug distribution at micrometre resolution. They will validate these predictions against a preclinical model that combines imaging with tissue staining for hypoxia. If successful, the work could produce structural biomarkers—measurable features of the tumour’s vasculature—that allow clinicians to personalise radiotherapy dose and drug selection for each patient, rather than treating all glioblastomas identically. This is fundamental science with a clear translational path: understanding how tumour architecture governs treatment delivery at the microscale.
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microKinetic sets off to revolutionise the treatment of glioblastoma multiforme (GBM) by delivering a radically new approach to the discovery of treatment biomarkers. GBM is the commonest primary brain tumour in adults, with a dismal median survival unchanged over 15 years. Tumour microenvironment is a key driver of chemoradioresistance. However, there are no spatially resolved microenvironmental biomarkers associated with prognosis and treatment response prediction, and any undertreated disease remains the single point of failure. For example, radiotherapy is delivered agnostic to tissue oxygenation, and investigational drugs are selected on dichotomous criteria for brain penetration, without considering variable pharmacokinetics (PK) via aberrant vasculature. microKinetic will address 4 key gaps in GBM understanding. The first is: how to structurally phenotype tumour vasculature and its temporal evolution? In response, microKinetic will formulate the first-ever method, based on Graph Theory, suitable for in vivo settings. Secondly, how to infer tumour tissue oxygenation and PK at sufficient resolution to improve treatment? Leveraging computational methods recently developed by me to calculate tissue oxygenation and PK from biophysical first principles, microKinetic will enable inference at the micrometre scale. Thirdly, how to thoroughly calibrate and validate computational predictions of oxygen and drug transport? microKinetic will validate predictions in a preclinical model of GBM combining structural and PK imaging, and hypoxia histology. Fourthly, we lack clinically accessible predictors of tumour tissue oxygenation and PK. microKinetic will be in position to investigate, for the first time, spatial correlations between coarse-grain vascular structure, tissue oxygenation and drug penetration. Such structural biomarkers (measurable in patients through biopsy or next-generation imaging) have the potential to become a transformative tool for personalised cancer treatment planning.
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