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New drug targets treatment-resistant cancer (2011)

A new drug targeting an important group of cancer cells attracted international funding in 2011 and will soon enter clinical trials.

2011 Highlight 01 New Drug Targets Treatment Resistant CancerLearning how to eliminate cancer cells that are resistant to current treatments is one of the biggest challenges in cancer medicine. One of the ways cancer cells can become resistant to treatment is through low oxygen levels (hypoxia).

These hypoxic cancer cells are the target of a new drug produced at the Auckland Cancer Society Research Centre (ACSRC) by Maurice Wilkins Centre investigators Associate Professor Michael Hay and Professor Bill Wilson with Drs Kevin Hicks, Frederik Pruijn and Jingli Wang. An agreement with Cancer Research UK will now allow the drug to begin clinical trials in the United Kingdom.

Tumours often have a haphazard blood supply and, as a result, zones that receive less oxygen than normal. “Hypoxia occurs in most types of solid tumours, but not necessarily in every patient with a particular tumour type,” says Michael. “Hypoxic cells in solid tumours are generally resistant to standard cancer therapies and currently there is no effective treatment for these cells.”

To cope with hypoxia, the cells also undergo genetic changes that make them more aggressive, more invasive, and consequently more able to spread around the body. So once other cells have been eliminated by chemotherapy or radiation therapy, they may go on to re-establish the tumour – which may now grow even more vigorously.

The new drug, named SN30000, kills cancer cells by damaging their DNA. It is a “prodrug” designed to be given to patients in inactive form and “switch on” only when it encounters hypoxia. It is intended to be given with chemotherapy or radiation therapy, eliminating hypoxic cells that would otherwise survive those treatments. It differs from other hypoxia-targeted prodrugs under clinical evaluation in its superior ability to penetrate hypoxic tissue and efficient activation even under relatively mild hypoxia in tumours.

ACSRC scientists have pioneered the use of hypoxia as a means of selectively targeting tumours and eliminating hard-to-treat cells. SN30000 is one of the results of a broad research programme over ten years that began with a National Cancer Institute grant to support a collaboration between scientists at Stanford University and the ACSRC.

“This work has been underpinned by sustained investment in cancer research by a number of government and charitable funding agencies. It’s been a privilege for the Maurice Wilkins Centre to help fund the latter stages of this research to the point where it can potentially help patients,” says Maurice Wilkins Centre Director Professor Rod Dunbar.


Image: Fluorescence imaging of a tumour showing areas of hypoxic tissue (red), tissue with a normal level of oxygen (dark) and blood vessels (blue). Image courtesy of Ms Annika Foehrenbacher, Experimental Therapeutics Group, Auckland Cancer Society Research Centre.