Kiwi scientists are combining leading cancer drug therapy research with cutting-edge computer modelling to create a simple system that could speed up the development of treatment agents.
Scientists from the world-renowned Auckland Cancer Society Research Centre (ACSRC) at the University of Auckland and the Auckland Bioengineering Institute have began a project described as having "enormous" potential well beyond the country's shores.
The team, led by oncology scientist and ACRSC senior research fellow Dr Kevin Hicks, aims to create a model which can be used to digitally test anti-cancer agents to extents never seen before.
Anti-cancer agents presently fail at very high rates when they reach the clinical development stage, and a key reason behind the slow progress of drug development is that the three dimensional structure of tumours isn't accounted for.
Most drugs are tested in tissue culture using single cells or cell monolayers, but these do not represent critically important changes in cell physiology due to the position in the tumour.
Dr Hicks and his research team have already demonstrated they can predict anti-tumour activity of hypoxia activated prodrugs, designed to reach those cancer cells which are found further away from the blood vessel, require less oxygen and are more resistant to radiation treatment.
"Most of the other models would assume that the cancer is like a well-mixed compartment, so that it equilibrates rapidly within the blood, and there is no transport difficulty between the blood and the deepest cells on the tumour," Dr Hicks said.
"Our success with the previous model was to include this transport factor in it - that allowed us to predict the activity of a number of compounds in a series, and then to go and use that to select the best compound for advanced testing."
That compound is currently under advanced testing in the UK, and likely to go into clinical trials within the next year or so.
Now, with a recently awarded Marsden Fund grant of nearly $774,000, this work would be extended, particularly to include the time dependence of drug and radiation effects, and the consequences for tumour growth.
To map this out, Dr Hicks and colleague Professor Bill Wilson have teamed up with senior scientist Dr Gib Bogle of the Auckland Bioengineering Institute, which leads the world in developing computer models of organs.
The result, Dr Hicks said, could be a simple but sophisticated computer model that could test a variety of drugs in a range of environments, and allow some to be weeded out before they got to clinical development.
"It's not going to eliminate all of the experimental work because you've still got to know how fast your drug diffuses and how it kills cells," he said.
"But once you've got that experimental information, you can put it into the model and look at differences in concentration, timing and what their effect is going to be on cancer cell killing, and how fast the cancer grows back."
The project is just one piece of promising research underway at the ACSRC.
A team led by Associate Professor Bob Anderson received a Marsden Fund grant of $847,826 for an investigation into how to improve the outcome of radiation treatment for cancer.
About half of all cancer patients who present with solid tumours receive radiotherapy, and a common cause of failure in this treatment was the resistance of hypoxic cancer cells, along with the increased risk of metastatic spread.
A key part of the research focussed on "masked" chemotherapy that could be activated directly by the radiation beam inside the resistant hypoxic regions of tumours, exploiting a powerful radical chain reaction discovered by the team.
Another recent study revealed that an intervention used to counter the neurotoxic effects of a chemotherapy treatment was ineffective, leading to its withdrawal.
This resulted in big savings in cost and treatment time at Auckland City Hospital's medical oncology service, one of the largest cancer treatment centres in Australasia.