Fighting cancer on the home front

CANCER RESEARCH:IT IS MORE than 40 years since US president Richard Nixon first declared a war on cancer when he signed the National Cancer Act of 1971. The act was meant to galvanise worldwide research, led from the US, into finding a cure for cancer, the scourge of the modern age when people are living so much longer. There was heady talk of a "cure for cancer" by the time of America's bicentennial in 1976.

Four decades on and the picture for cancer victims is decidedly mixed. Some six million people die worldwide from cancer every year, most of them in the developed world.

The recent deaths of Brian Lenihan Jr and Apple founder Steve Jobs provide a sobering reminder that cancer is no respecter of age or worldly success; even the best treatments are often inadequate when faced with such a dreadful illness.

There have been notable successes, most significantly in childhood leukaemia, where success rates are close to 90 per cent; in prostate cancer, which has been turned from a deadly disease into a chronic illness; and in breast cancer.

Billions are spent every year on cancer research internationally. The US government-funded National Cancer Institute (NCI) spends between €3.5 billion and €4 billion alone on cancer research.

The biggest cancer charity in Europe is Cancer Research UK, which has an annual budget of £425 million (€512m).

Closer to home, the Irish Cancer Society has given more than €30 million for research projects in Ireland.

There has been much criticism that efforts to cure cancer have been meagre given the money spent on research, but the Irish Cancer Society’s head of research, Prof John Fitzpatrick, formerly of the Mater and UCD, says these criticisms underestimate the scale of the challenge involved.

“Our understanding of the mechanism of cancer and the causes of cancer has gone up exponentially,” he says. “The introduction of new therapies has taken a lot longer.”

Since the discovery of oncogenes – gene mutations that cause cancer – in the late 1970s by Michael Bishop and Harold Varmus, for which both won the Nobel Prize for Medicine, researchers have pioneered therapies that focus on the particular gene abnormality that causes the cancer.

Last month, Dr Dennis Slamon, the man who developed Herceptin, the drug which has saved the lives of hundreds of thousands of women with breast cancer worldwide, visited a collaborative research project being carried out in Dublin. He says that when he started in 1986, they could look at only one gene at a time.

“Today, the people in my laboratory in Los Angeles and here in Dublin can look at 28,000 genes overnight. That’s how fast the technology has moved.”

Herceptin has a radical impact on women who over-produce or “over-express” the protein HER2, which causes breast cancer cells to grow out of control.

Similar treatments have been slow in coming but are now making a real difference. Imatinib, better known as Gleevec, has had a dramatic impact on chronic myeloid leukaemia, which was once a fatal disease.

Crizotinib is proving to prolong the lives of those have a certain type of lung cancer, which is among the deadliest of all cancers. It is being pioneered in a certain subset of patients at St James’s Hospital under the supervision of Dr Ken O’Byrne, a world expert in the field.

Malignant metastasised melanomas have a gene called B-RAF. Specific therapy drugs, target this gene and so are making a difference to patients who would otherwise not survive.

Ireland punches above its weight in cancer terms because of the All-Ireland Cooperative Oncology Research Group (Icorg). The group was set up in 1996 by Prof John Crown among others. In 2000 it expanded to include Northern Ireland.

It is unique in the world that it can draw on every Irish cancer patient who is eligible for drugs trials. There are approximately 7,500 such patients, and almost every oncologist in Ireland is signed up to it. Irish patients were among the first to get Gleevec and Herceptin. They are also getting Crizotinib – and 60 per cent of the patients are still alive two years later.

“Irish patients are getting drugs such as Gleevec years before they would normally be made available because of Icorg,” says Prof Crown. “There are a lot of people alive who got medicines through Icorg who would be dead otherwise.”

Dr Slamon came to Ireland to review some of the work being carried out by Prof Crown’s Molecular Therapeutics for Cancer Ireland (MTCI) group, which is testing treatments for cancer, and Icorg, which is providing patients for clinical trials. He is working with Prof Crown.

“They are doing real fine research,” Dr Slamon says. “There’s no question that there is great research going on in Ireland. That’s why we are collaborating with Dr Crown’s group.

“In both Herceptin and Labatinib, the other HER2 drug, they were involved in early research, and also in research for non-HER2 positive disease.”

A major international breakthrough was made by Prof Michael Joe Duffy at the UCD Conway Institute when he developed a test for predicting whether women with early-stage breast cancer are at high risk of developing metastasis or secondaries, and whether or not they need chemotherapy. The marker is now recommended by several expert groups in Europe and the US for testing on women with newly diagnosed breast cancer.

Prof Fitzpatrick concedes that the amount of money available to Irish researchers is “nowhere near” that which is available in the US, so Irish consortia have made a virtue of necessity.

The bulk of Irish research is looking at prognostic biomarkers that should tell if that person to going to respond to certain types of treatments, for example the manner in which HER2-positive patients respond to the Herceptin drug.

“The cancer each person gets is unique to that person or unique to a group of people,” Prof Fitzpatrick explains. “In Ireland, because of the limited resources, we have to galvanise these resources, and the way to do it is with collaborative research.”

The Irish Cancer Society funds several research programmes looking at prostate cancer through the Prostate Cancer Research Consortium. For example, PCRC researchers have identified a new panel of biomarkers which could be used to help diagnose the illness earlier.

Dr Antoinette Perry of Trinity College Dublin is leading a team looking at new biomarkers which will more accurately predict if a patient has non-aggressive prostate cancer which is confined to the gland itself, or prostate cancer, which extends beyond the gland itself.

Her team is looking at biomarkers that are more accurate than the present Prostate-Specific Antigen (PSA) test and can be detected in blood or urine rather than the invasive PSA test. The work, which is being carried out at St James’ Hospital, has attracted funding not only from the Irish Cancer Society but also from the US-based Prostate Cancer Foundation.

The best research will always get money from overseas and that is what is happening with several Irish cancer research projects. Last week the Irish Cancer Society honoured some of its researchers in its first annual award ceremony.

“Irish research is highly regarded. We have top-class researchers and top-class brains and we get invited to present at big cancer research conferences,” says Prof Fitzpatrick.

The excellence in cancer research is not just confined to this side of the border. The Northern Ireland Comprehensive Cancer Services (CCS) programme received an honour recently from Queen Elizabeth II. It has linked therapeutic approaches for patients with cancer sufferers and has involved local companies such as Almac to deliver new drugs and diagnostic treatments.

The ultimate goal of all cancer research is not only to save lives but to provide diagnostic tools and treatments which can provide employment at home. The CCS programme has been credited with saving the lives of between 50 and 60 people in Northern Ireland every year who have cancer. Northern Ireland has some of the best survival rates from cancer in the UK.

Dr Crown says his ambition is to create a virtual Irish Cancer Centre. He believes the idea of a bricks-and-mortar centre is “Victorian thinking” and Icorg showed that a virtual centre can work, as exemplified by the success of the MTCI, which involves most universities in Ireland, along with pharmaceutical companies. He and others will be submitting a proposal to Science Foundation Ireland to fund an Irish cancer research institute, but it would not be based in any one place.

“We are 70 per cent there,” he says. “We need everybody to check in their institutional chauvinism at the door and realise that there is no individual place that good, that we are better off progressing together. Collaboratively, we can make this work.”

SOME RESEARCH PROJECTS CARRIED OUT IN IRELAND

BREAST CANCER

St Vincent’s Hospital Dublin Researchers are examining why some HER2-positive patients do not respond to Herceptin. In Beaumont Hospital they are looking at how breast cancers become resistant to treatment. Research is also being carried out in TCD as to why breast cancer cells need more sugar than normal cells.

OESOPHAGEAL CANCER

Prof John Reynolds is helping co-ordinate research into how a condition called Barrett’s oesophagus can develop over time into oesophageal cancer.

LUNG CANCER

A study carried out at St James’s Hospital in Dublin has discovered the impact that two blood-clotting enzymes

have on lung cancer cells. One, thromboxane synthase, promotes the growth of the cells. The other, prostacyclin synthase, inhibits that growth. Switching one on and the other off could improve the life expectancy of lung cancer patients.

LEUKEMIA

Researchers at University College Cork are examining how changes in a gene can turn a normal cell into an aggressive cancer cell.

OVARIAN CANCER

Researchers at UCC are looking to identify cell proteins that encourage the spread of ovarian cancer cells to other parts of the body, to help research that might lead to the development of drugs that prevent the spread of these cancer cells.

PROSTATE CANCER

Under a programme funded by the Irish Cancer Society, Prof William Watson, based at University College Dublin, is leading a major programme of prostate cancer research involving collaboration between researchers in Ireland and abroad. This programme aims to develop a defined panel of biomarkers which can be used to identify those patients who do not need to undergo radical treatment for their disease.

Prof Caitriona O’Driscoll of the School of Pharmacy, University College Cork, is looking at better ways of delivering cancer treatments for prostate tumours. Her research is specifically looking at finding ways to improve “gene therapies” for prostate cancer.

Prof Ciaran Morrison, based at the National University of Ireland, Galway has been involved in DNA damage research for a number of years. He is now using his knowledge in this area to improve the effectiveness of radiation therapy for prostate cancer as this involves killing the cancer cells by DNA damage.

Dr Laura Barkley-Elliman’s research involves a new set of molecules called microRNAs within the cell which may be involved in the development of cancer.

She is looking at specific microRNAs to see if they play a role in the development of prostate cancer.