Intrinsic and Acquired Resistance to Anti-angiogenic Treatments: Interaction between Tumor Vascular and Adaptive Metabolism

Supervisor: Dr. Eugene Wong

Project Description (Abstract):

Molecularly targeted therapy is fundamentally different from cytotoxic chemotherapy. For solid tumors, these therapies are predominantly cytostatic, not cytotoxic. The clinical transformation in targeted therapy requires an equal transformation in the methods of assessing individual’s response to these drugs and investigating tumor adaptation. Imaging tumor perfusion (not volume) for anti-angiogenic treatments would be equivalent to imaging tumor volume for chemotherapy. While modifications in cytotoxic chemotherapy keep toxicities at an acceptable level, it may come at the expense of tumor control. An appropriately adjusted anti-angiogenic drug dose can reduce the severity of induced tumor hypoxia while at the same time prevent development of resistance. Heterogeneity in solid tumors and the multitude of redundant pathways allow cancer cells to adapt and survive under stress. Such adaptation can be measured and modelled. Within a multidisciplinary group, we are investigating the adaptation of cancer metabolism and its spatiotemporal variations, computationally and experimentally. This project will focus on the computational aspect of modeling oxygen, glucose and lactate transport within a tumor based on high-resolution micro-CT scan of the tumor vasculature. Intra- and extra-cellular compartmental modeling of glucose and lactate will be implemented as a function of the amount of their cellular membrane transporters to examine how cancer metabolism adapt to changes in tumor blood vessels.



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