Conquering cancer: Shining light in battle for hope

By Martin Johnston

Cancer is the leading killer of New Zealanders, but there is an enormous effort going on here and overseas to find more effective treatments. Herald health reporter Martin Johnston today begins a two-day series looking at some of the drugs being developed at a world-renowned scientific discovery unit, the Auckland Cancer Society Research Centre.

• The Auckland Cancer Society Research Centre is a scientific unit devoted to discovering and developing new drugs to treat cancer
• The Conquering Cancer open day will be held on Saturday, 9.30am to 3pm, at the Auckland Cancer Society Research Centre
• People wishing to donate to the Cancer Society can visit cancernz.org.nz or donate or call (09) 308 0172

Auckland is home to a scientific research centre that has developed an enviable international reputation for producing new cancer drugs that get picked up for international clinical trials.

The Auckland Cancer Society Research Centre, based at the University of Auckland, this year celebrates its 60th anniversary. Its scientists have designed 10 new cancer drugs that have reached at least a phase one trial in humans. Some have gone much further and one has made it all the way, becoming a registered medicine to treat leukaemia.

It has also got two non-cancer drugs into clinical trials. Four other new-drug projects, three of which are for cancer, are nearing either their first trial, commercial agreement with a trial partner or final selection of the best drug candidate.

Ten reaching human trials may seem few to an outsider, but each drug can occupy decades of researchers' careers, generating vital new knowledge.

Cancer drug development is an expensive and in some ways fickle business. The great hopes placed in a drug can vapourise when a trial flops, as happened with DMXAA.

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The centre's director, Professor Bill Denny, says it is one of the world's most productive academic units in charities or universities for producing new cancer drugs. The other is the London-based Institute of Cancer Research.

"Some of them are bigger than us but most ... focus on basic research rather than trying to get the drugs into the clinic. I would have thought in an absolute sense we are the two top academic units in the world for delivering drugs to clinical trials."

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Health Research Council chief executive Professor Kathryn McPherson says New Zealand carries a big international reputation in cancer research.

"It is one of our strongest performing areas. If you look at high-quality publications, that too is an indication that we punch way above our weight in cancer research, such as the work that group [the Auckland centre] does.

"The HRC is very proud of the work these groups do. Not just one project; all the work together. They are making a real difference to health care and the potential for new treatments in cancer. They are certainly a very strong group and generally our cancer researchers are fantastic in New Zealand. We really are the best in the world in cancer research."

The Auckland centre's only drug to become registered by regulatory authorities -- in the early 1980s -- is the leukaemia therapy Amsacrine, the first drug of its kind to be successfully trialled. The centre developed three others which target the same aspect of cancer and which also reached human trials.

"One of the problems with doing early, novel stuff is that there are a lot of failures along the way," says Professor Denny. "We've had drugs enter phase one, phase two, phase three large-scale trials, but getting them ... into registration is another hurdle again. We are bringing new drugs into trial, getting new entities, new types of compounds, where you are delivering information as well to the drug development community."

The centre is at the front line of drug developments that use the immune system's own cancer-killing abilities, exploit low oxygen levels -- hypoxia -- in tumours, or target molecular signal pathways.

One of its hypoxia-activated drugs, Tarloxotinib, has entered phase 2 trials in Australia and the United States in patients with certain types of lung cancer and head-and-neck cancers. Another project to develop a so-called hypoxia "prodrug" -- a drug which only becomes toxic inside a tumour, reducing side effects on healthy tissue -- is in the final stages of the researchers choosing a "lead compound", their best bet to promote for clinical trials. A third project, an immunotherapy drug which targets IDO1, an enzyme used by tumours to evade the immune system, is in negotiations for a biotech company to take it into human trials.

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More than 1200 scientific papers have been published by the centre's staff and they have applied for 100 patents. It employs around 80 staff and runs on a budget of about $12 million a year, around $2.4 million of which comes from the Auckland-Northland division of the Cancer Society, the national charity which raises money from its annual Daffodil Day.

The core funding from the society is critical, Professor Denny says, giving the centre a "leg up" in applications for grants from charities and contracts with biotech firms. The centre's drugs have also led to creation of three spin-off companies, one of which had raised about $50 million. But the model has changed.

"Forming a company used to be the way to go. Now, it's waiting till you have got a product interesting enough for [a company] to get on board. We have three drugs, three projects at the moment fairly close to being partnered. But until they are partnered, it hasn't happened."

'Miracle drug' flop shows up the risks

Auckland-designed drug DMXAA was considered such a bright hope it was pitched as a "billion-dollar New Zealand success story" in a 2009 report promoting the importance to the economy of the therapeutics industry.

But only months later the anti-cancer drug described as a miracle had flopped in a big phase-three clinical trial, failing its test of effectiveness in lung cancer patients. Later, in 2010, a second big trial was stopped early because using the drug with chemotherapy was considered unlikely to prolong patients' overall survival.

It was a hard landing for the high-flying DMXAA, also called vadimezan, a result of research which began at the Auckland Cancer Society Research Centre in 1986.

In 2006, phase 2 trial results had appeared to show the drug, designed to destroy the blood supply of tumours, extended patients' survival.

It had been picked up by British firm Antisoma and international pharmaceutical company Novartis signed up for phase-three trials. Novartis licensed the drug from Antisoma in 2007 in a deal valued at US$800 million ($1.163 billion), in what the NZBio report on the human therapeutics sector said was "the biggest drug licensing deal in the world that year".

Novartis wouldn't have had to pay the full fee, but was estimated to have spent well over US$100 million.

The DMXAA story shows what a gamble drug development can be.

The research centre's Professor Bill Wilson said it was unlikely DMXAA would be resurrected, although subsequent work on it had suggested reasons why it hadn't worked.

"In the process, as an academic drug-discovery group, you are learning about the nature of the target, the nature of the tumours, as well as the molecules [the drugs].

"Even if the drugs ... don't achieve what we want, we learn a great deal in the process and it is the generation of new knowledge that is at least as important from our point of view."

The research centre

The Auckland Cancer Society Research Centre, based at the University of Auckland, is a scientific unit devoted to discovering and developing new drugs to treat cancer. It also runs clinical trials of its own and other organisations' drugs. A fifth of its funding comes from the Auckland/Northland division of the Cancer Society, a charity.

The Conquering Cancer open day will be held on Saturday, 9.30am to 3pm, at the Auckland Cancer Society Research Centre. Entry is free. More than a dozen short talks will be offered that give a glimpse into the work of the centre's researchers. On Thursday April 14 at 6.30pm, Canadian cancer researcher Professor Ian Tannock, of the University of Toronto, will give a free public lecture at Auckland University.

People wishing to donate to the Cancer Society can visit cancernz.org.nz or donate or call (09) 308 0172

- NZ Herald

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