Leading the way in battle on cancer

YOUR HEALTH:Through collaboration, Ireland could become a hub of cutting-edge cancer research, says a newly returned expert

IRELAND IS well positioned to become a world leader in the development of anti-cancer therapies,according to an Irish haematologist at the international forefront of pioneering new treatments.

In addition, Irish cancer patients will no longer have to travel abroad for access to clinical trials for difficult-to-treat diseases, says Prof Frank Giles, who after 18 years in the US is returning home to take up a unique role here.

Prof Giles is a leading international investigator in the ongoing assessment of Tasigna (nilotinib), one of the fastest drugs in US history to move from chemical synthesis to Food and Drug Administration (FDA) approval.

Tasigna is now thought to represent a significant step towards a cure for chronic myeloid leukaemia (CML), a disease which affects about one in 100,000 people. Forty years ago, a diagnosis of CML meant a survival rate of close to zero – today, the rate is more than 95 per cent.

From tomorrow, Prof Giles will take up a joint position on the innovative new cancer research units at NUI Galway and Trinity College Dublin as a professor of cancer therapeutics.

The researcher, who has been based at the internationally-acclaimed University of Texas Health Science Center at San Antonio, will retain his post there as adjunct professor of medicine. He intends to use this three-way structure to optimise collaboration in the field of cancer care.

Tasigna’s initial 2007 indication was for CML in adult patients whose disease had progressed or who could not tolerate other therapies, including the gold standard intervention Glivec (imatinib). However, many researchers, including Prof Giles, believed Tasigna was potentially superior to Glivec, the parent drug from which it was initially derived.

In June of this year, the FDA completed a six-month review of Tasigna and expanded its indication to a first line treatment for adults in earlier stages of CML. Pending regulatory submissions have also been filed in the EU, Switzerland and Japan.

Prof Giles says the FDA decision was of global significance – both in terms of progress towards curing this rare form of the disease and, in broader terms, of establishing new paradigms for anti-cancer drug development.

A major follow-up study of Tasigna, the ENESTnd study, is currently being conducted at 217 global sites – with very impressive results. Other studies of the drug in patients newly diagnosed with CML are ongoing, including an important Irish-designed and led international study. The latter made headlines late last year when its participants were among the first in the world to receive Tasigna at the new FDA approved dose.

The Irish study is being led by two haematology teams – one at University College Hospital Galway, under Prof Michael O’Dwyer, and another at St James’s Hospital, Dublin, under Dr Eibhlin Conneally – with the support of the Irish Clinical Oncology Research Group (ICORG). It has attracted participation from centres outside Ireland including in Britain and the US.

Prof Giles remarks that Glivec itself had been a truly paradigm-shifting drug that had ushered in a new era of truly safe targeted anti-cancer therapy.

“We thought it would be extremely difficult to develop an agent that could demonstrate, in an increasingly rigorous scientific environment, unequivocal superiority to Glivec,” he says. “Tasigna is that superior agent. Its use in newly diagnosed patients with CML is a major step towards cure of a once uniformly fatal leukaemia. Its development has taught us vital lessons in how to approach novel anti-cancer agent development in a way that, I am certain, will accelerate meaningful advances across the entire spectrum of human cancer.”

However, while the development of a successful drug is of huge importance to CML patients, Prof Giles makes the point that this is just one drug and one type of leukaemia. There is a lot more work to be done in cancer research.

“Quite frankly, I would settle for a fraction of the success we have had with Tasigna in other cancers I’m dealing with, especially solid tumours and other leukaemias,” he says. “CML has become the ‘poster child’ for targeted cancer therapy, proving that a precise understanding of the cause of a disease allows an effective therapy to be developed if you keep pushing away at it.”

He adds that it’s not just the development of new drugs that provides hope for the future of cancer treatment. Promising research is also taking place in other areas.

“Some studies are looking at modified viruses. These are quite clever, targeted things which could potentially be very powerful anti-cancer weapons if we can teach them to go where we want them to.

“There are also a lot of people making advances in teaching the immune system to attack cancer, once it has been brought below a reasonable threshold with conventional medicine.”

The development of Tasigna epitomises what can be achieved through collaboration, according to Prof Giles. He believes Ireland is well positioned to play a leadership role in international anti-cancer collaborations.

“Just because Ireland doesn’t have an enormous population does not mean we can’t be involved in clinical anti-cancer agent development,” he says. “We are already involved in collaborations with some of the major sites of early anti-cancer therapy development, predominantly in the UK and Europe, including Cardiff, Liverpool, Bologna and Berlin.

“We can compensate for our lack of numbers by creating collaborative groups with these large sites. Europe is really coming to the forefront in the development of anti-cancer agents and we plan to further strengthen our links with these sites.”

A research group in Trinity College has already come up with a compound ready for testing in humans as an anti-cancer agent. Meanwhile, in NUI Galway, there is a lot of early work being done on stem cells, which have the potential to evolve into anti-cancer therapies.

“The new clinical research units in Galway and Dublin give us the physical space, staffing and infrastructure,” says Prof Giles.

“Most importantly, they create a culture of clinical research and development. Many Irish doctors who practice abroad help people in Ireland to gain access to care outside the country, particularly in very difficult-to-treat cancers. This is something we hope to reverse very quickly.” Instead, people would be coming to Ireland to access cutting-edge treatments.

Next month, a landmark phase-one trial into a first generation anti-cancer drug is due to begin at the cancer research unit in Galway under Prof Michael O’Dwyer, with plans to expand it to Trinity College and beyond.

Prof Giles is particularly excited at the opening, as it is the first trial of its kind in Ireland. It will focus firstly on leukaemia, but is also likely to be applicable to a large number of solid tumours.

So, why did Prof Giles choose to return to an Ireland in recession after so many years of successful research and practice in the US?

“A lot of people I have a lot of respect for have been coming home quietly over the past few years, so there is now a critical mass of talent in Ireland,” he says.

“Scientists from Ireland are doing well all over the world. My hope is that, over the next decade, we can create an environment they feel they can come home to – not just as a personal decision but because it is academically attractive for them.

“They are working in places that are inevitably much more highly-resourced than Ireland, particularly the US. However, by further integrating ourselves into pan-European research collaborations, I firmly believe we can overcome the fact that resources here are more limited.”