Therapeutic targeting and clinical assessment of the tumour vasculature

• Main Author: Ng, Quan Sing
• Published: University College London (University of London) 2008
• Subjects: 616.99407548
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500122

The tumour vascular network is essential for tumour growth. Over the next few years, the use of vascular targeting drugs in the treatment of patients with cancer will escalate, which in turn will increase demand for non-invasive methods of assessing tumour vasculature. A perfusion CT technique was developed, allowing measurement of tumour vascular leakage (K) and blood volume (BV) of entire large tumours. This technique is shown to improve on measurement repeatability compared to conventional single level techniques, and can be used to measure tumour vascular changes following anti-cancer treatment. Ionising radiation has been shown to act synergistically with the vascular disrupting agent Combretastatin A4 Phosphate (CA4P) in animal tumour models. Patients with advanced non-small cell lung cancer were treated with fractionated radiotherapy in combination with CA4P. Radiation alone increases tumour K and BV, especially at the tumour rim, and appears to enhance the vascular disrupting activity of CA4P. The increase in K after radiotherapy correlates with subsequent decrease in BV after CA4P, and a sustained reduction in tumour BV was achieved with this combination. Nitric oxide (NO) is an important signalling molecule responsible for maintaining the vasodilator tone in tumour vessels, as well as having pro-angiogenic properties. As part of a phase I study, patients with cancer were treated with the nitric oxide synthase inhibitor N-nitro L-arginine (LNNA). Patients with measurable tumours were scanned using perfusion CT, and all patients demonstrated sustained reductions in tumour BV, demonstrating for the first time in man that NO inhibition has tumour anti-vascular activity. In summary, perfusion CT is a repeatable technique that can be used to measure vascular changes in whole tumours following therapy. The results presented here have provided further evidence that targeting the tumour vasculature is a promising approach in the treatment of cancer.