Grant: Operating Grant

A new class of therapies target the developing (or 'angiogenic') blood vessels of a cancer, which both deliver oxygen and nutrients essential for tumour growth and provide a pathway for its metastatic spread. Antiangiogenic drugs inhibit the signals that tumours send to the host to stimulate growth of such new vessels. However, many patients develop resistance to these treatments: the proposed research develops and applies imaging methods designed to monitor response of cancer blood vessels to such treatments so as to aid in their improvement. We will image blood flow in both animal models of cancer and patients with renal cell carcinomas under therapy to investigate how this response changes as resistance develops and whether imaging can successfully predict its onset. Imaging measures of blood flow will use contrast-enhanced ultrasound and magnetic resonance imaging, aligned to register the same tissue and extended to cover the three-dimensional volume of a tumour. Measurements will be compared to biological markers of tumour activity, helping elucidate how resistant tumours evade antiangiogenic treatment and enabling assessment of new therapeutic approaches. The aim is to help develop strategies to delay the onset of resistance in patients undergoing antiangiogenic therapy and provide new clinical instruments for serial noninvasive assessment of their efficacy.