A Prostate cancer ”triple whammy drug“ passes first test hurdle
A “triple whammy” drug that tackles advanced prostate cancer in three different ways has passed its first hurdle. Scientists reported promising early trial results on galeterone, which is designed to treat cancer that no longer responds to hormone therapy.
The drug reduced levels of Prostate Specific Antigen (PSA), a prostate cancer blood marker, by 30% or more in around half of patients.
Eleven patients had PSA reductions of 50% or more, and in some there was significant shrinkage in tumour size. A total of 49 patients took part in the Phase I study, which primarily looked at safety and dosing levels.
All had “refractory” or “castration resistant” cancer that has ceased to respond to hormone therapy aimed at preventing tumours being fuelled by testosterone.
Currently there is little doctors can do to help prostate cancer patients who progress to this stage.
Galeterone works in three ways, by blocking “receptor” proteins that respond to testosterone, reducing the number of receptors in tumours, and targeting an enzyme linked to hormone pathways called CYP17.
Trial leader Dr Mary-Ellen Taplin, from Harvard Medical School in the US, said: “Because currently available therapeutic options to treat castration-resistant prostate cancer are limited, often poorly-tolerated and may fail because of resistance, patients are in urgent need of new safe and effective treatments. These Phase I galeterone data, demonstrating minimal toxicities, improved PSA response and a reduction in tumour size, are exciting for those of us in the medical community treating this life-threatening cancer.”
The findings were presented at the annual meeting of the American Association for Cancer Research (AACR) in Chicago.
A larger Phase II trial focusing on the drug’s effectiveness is planned later this year.
Angry householders in their thousands protest against the household charge in Dublin
ABOUT 5,000 vehement, loud and persistent demonstrators rallied outside the Fine Gael ardfheis, protesting against the €100 household charge over the weekend.
Kept back from the convention centre in the Dublin docklands by barriers and gardaí, demonstrators held up placards with a range of messages: “No tax on my jax”; “When the bankers pay we will pay”; “Enda 1994: This is a vampire tax. Well suck up, no, no, no”; “Póg mo Hogan”; and “Final reminder: no way Hogay.”
At times chanting “can’t pay, won’t pay” and “out, out out”, some protesters shouted “shame on you” as Fine Gael delegates tried to get past the demonstration and into the convention centre.
Kilkenny councillor Billy Ireland said he was kicked and hit in the ribs. Another woman said “we have a right not to be pushed and shoved and manhandled trying to get in there. Only for that guard saw me, I was on the ground.”
A man who looked like Minister for the Environment Phil Hogan was jostled and pushed to the ground by a small group of protesters, some carrying Éirígí anti-charge posters. The man said repeatedly, “I’m not Phil Hogan, they’ve got the wrong guy.”
He was helped into a Garda car which was rocked by some protesters before it moved away.
Socialist Party TD Joe Higgins, Socialist Cllr Ruth Coppinger and People Before Profit TD Richard Boyd Barrett addressed the rally. Independent TD Luke “Ming” Flanagan also attended.
Almost 25 others also spoke, including Liz Feighan from Cork, who read an open letter to the Taoiseach: “€100 might not mean much to you but to me it’s five weeks’ electricity bill or a week’s grocery bill. I used to go to one supermarket, now I’ve got to go to four. Every cent . . . counts.”
Oliver Nolan, who is homeless, said: “We’re conditioned to be more scared of the homeless man on the street than the man in the suit, and yet the suits are the ones that robbed us blind.”
The household charge wasn’t the main issue for a number of people. Denis Scannell, from Listowel, Co Kerry, said: “I’m a farmer and they’re stopping me cutting turf. I might have paid the household charge only for that.
“I think the people in Ireland kneeled down too long. We had to come out when we see what’s going on at the top – the Mahon tribunal coming out with ‘He didn’t tell lies, he told untruths’.”
Sheila Byrne from Malahide said, “I’m here because I want answers on Leas Cross as well.” She felt nobody was held accountable in relation to what happened in the Dublin nursing home, which was subsequently closeddown. Her father died there.
Breda Fitzpatrick from Malahide Road, Dublin, said: “I paid €37,000 in stamp duty seven years ago and I had to take out a separate loan for that, and I’m not paying another €100.”
At the ardfheis, Mr Hogan said, “I’ve tried my best to reflect the difficulties that people are going through; the vulnerable people and people that are on mortgages by exempting people on mortgage supplement.
“Nobody wants to be imposing a tax at a time of austerity, but we are where we are in terms of the agreements that we’ve entered into in order to draw down the money for local services.”
Over 40 years of research & fighting cancer and still there is no cure?
Since the discovery of oncogenes – gene mutations that cause cancer – researchers have pioneered therapies that focus on the particular gene abnormality that causes the cancer
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
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
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.
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