Selective Therapies Targeting Tumour Vasculature of Colorectal Liver Metastases

Funded Activity Summary

Cancer of the bowel is the second highest cause of cancer related deaths in Australia. Over 70% of these deaths are due to bowel cancer spread to the liver or liver metastases. Treatment options for the majority of patients with liver spread are limited. Although chemotherapies are a standard treatment option, they cause significant side-effects as they are small in size and thereby distributed to both cancer and normal tissue. Given the limitations of chemotherapy, our objective is to investigate two new strategies which selectively destruct tumours with minimal effect to normal tissues. Cancer growth is dependent on an efficient blood supply. One strategy uses drug delivery systems (DDS) to selectively target cancers by exploiting the unique properties of tumour blood vessels. The second strategy uses vascular targeting agents (VTA's) which act on tumour vessels to reduce blood flow and starve the tumour of oxygen, leading to its destruction. We will be testing two agents: SMA-Pirarubicin, a DDS and an innovative VTA, Oxi4503, in an animal model of colorectal cancer liver metastases. Although these drugs are successful in destroying the majority of tumour cells, they have a patchy effect and do not completely destroy the cancerous growth. The varied effects of these agents may be due to variations in tissue hypoxia, tumour vessel structure or factors which trigger blood vessel formation and breakdown. These features will be investigated using techniques established within our laboratory. We will also investigate the combined effect of other novel agents and hyperbaric oxygen administration to improve the effectiveness of these drugs. A successful outcome will result in the development of an improved treatment method which targets tumours, producing maximum destruction with minimum side-effects. This has the potential to replace standard chemotherapies as the preferred treatment for patients with bowel cancer spread, with overall significant patient benefits.

Funded Activity Details

Start Date: 01-01-2006

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $519,279.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Surgery

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

drug delivery systems | drug targeting | hyperbaric medicine | hypoxia | liver metastases | mechanisms | necrosis | novel anticancer agents | oxidative stress and apoptosis | tumour microvasculature

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