Saturday 21 July 2018

The cutting edge of cancer

Around the country there are teams of scientists, medics and researchers who are dedicating their lives to finding new and better ways of fighting the disease. Which of these breakthroughs are they most excited about?

Professor William Gallagher, a cancer researcher at UCD. Photo: Damien Eagers
Professor William Gallagher, a cancer researcher at UCD. Photo: Damien Eagers
Professor Bryan Hennessy pictured in the Smurfit building, Beaumont Hospital. Photo: Marc Condren

Ailín Quinlan

Putting the words 'optimism' and 'cancer' in the same sentence might appear paradoxical; as Robert O'Connor of the Irish Cancer Society says bluntly, we're unlikely to find a single cure for cancer in our lifetime.

But O'Connor, who is head of research at the ICS, believes that there are good grounds for hope thanks to ground-breaking cancer research, which in recent decades has brought enormous breakthroughs in all aspects of oncology diagnostics and treatment. And as the ICS prepares for its annual Daffodil Day fundraiser on Friday, a drive which provides significant funding for new research, it's a fitting time to look at how far we've come.

"Fifty years ago, for example, leukaemia in children was always fatal, often rapidly so," O'Connor observes. "Today the majority of children with leukaemia in Ireland will be taking part in clinical research and more than nine out of 10 of them will be fully cured of their disease.

"In testicular cancer, even in the most advanced stages, which are now rare, about 75pc of men will be fully cured and 19 out of 20 will be cured if the disease is identified in the increasingly more common early stages."

O'Connor is by no means alone in this assessment.

"I feel there are grounds for great optimism in relation to the effective management of cancer," declares William Gallagher, professor of cancer biology at UCD, who headed up the team of scientists that made international headlines last year following its discovery of a new way to treat an aggressive form of breast cancer.

"If we stand back a bit, we can see that huge progress has been made. It has been particularly driven by advances in biology," says Professor Gallagher, who adds that over the last 20 years, there has been "a revolution" in our understanding of how cancer works.

"Our improved understanding of the biological basis for cancer has spearheaded breakthroughs in new diagnostics and therapies."

* Precision Medicine and Targeted Treatments

The concept of 'precision medicine,' explains Professor Gallagher, refers to the use of targeted treatment to address a particular subtype of disease in a patient, rather than the traditional 'one size fits all' approach - and it's resulting in better outcomes.

"Where once we were dealing with chemotherapy and hormone therapy, now we have treatments for many cancers such as biologic agents," says Dr Conleth Murphy, consultant medical oncologist at the Bon Secours Hospital in Cork and senior lecturer in clinical education at UCC.

"There is also oral-targeted therapy or smart drugs which target a weakness or vulnerability in a cancer cell and exploit it.

"One very good example of this is a patient with lung cancer that has a specific mutation. We now have drugs to attack that mutation and they can offer much better results than chemotherapy."

Breast cancer is an excellent example of how targeted treatment can benefit patients, says Professor Gallagher.

"The shift is to a better focus on targeted treatments for women who need it rather than a generalised form of treatment.

"More targeted treatment yields better results, with often less toxicity," says Gallagher - who leads a nationwide Collaborative Cancer Research Centre focused on improved 'personalisation' of breast cancer treatment, Breast-Predict - which is supported by the Irish Cancer Society.

Professor Gallagher says that today, all breast cancers are assessed for biomarkers (biological indicators) in order to classify the type of tumour in a cancer; for example, HER2-positive, which accounts for about one-fifth of all breast tumours.

"This subgroup of breast cancers was traditionally considered very aggressive," he says. "However, a targeted approach was developed about 20 years ago which revolutionised the treatment of this type of breast cancer. It involves the use of drugs which target the HER2-positive cancer cells, basically destroying the tumour.

While this treatment approach has been effective in the clinic, he says that a subset of patients will relapse over time with resistant disease.

Work led by Professor Bryan Hennessy, of the Royal College of Surgeons in Ireland and Beaumont Hospital in Dublin, and supported by the Irish Cancer Society, has recently uncovered why this may occur in certain patients and has initiated a ground- breaking clinical trial called PantHER to overcome this problem, according to Professor Gallagher.

A second major type of breast cancer is ER-positive, which accounts for about two-thirds of patients, and is treated with hormone therapy in a targeted approach.

"Most patients with ER-positive breast cancer can do perfectly well with hormone therapy alone, particularly those with early-stage disease where it has not spread beyond the breast," says Professor Gallagher.

Traditionally - to potentially benefit the small subset of 7ER-positive patients who have a high risk of the disease spreading around the body (metastasis) - practically all ER-positive patients were given chemotherapy also.

However, Professor Gallagher adds, chemotherapy is a blunt instrument, leading to many side-effects. "The key clinical dilemma here is to avoid potential over-treatment of patients with chemotherapy that will not benefit them."

* OncoMasTR

With his colleagues at UCD and TCD, Professor Gallagher has developed a novel diagnostic tool called OncoMasTR, which can accurately identify breast cancer patients who have either a low or high chance of the disease spreading around the body.

This new tool is being developed commercially by a spin-out company, OncoMark, and is set to be available for patients before the end of 2018.

* Targeting Triple Negative Breast Cancer

A third group of breast cancer patients - or about 15pc of patients - are neither HER2-positive nor ER-positive. These patients fall into the Triple Negative group for whom the only option is chemotherapy.

"A lot of research is ongoing around the world into this group of breast cancers. It is called Triple Negative and is often found in young women with breast cancer. It is a particularly aggressive form of breast cancer."

However, ground-breaking research performed internationally and by Professor Gallagher's team, has found a new way of targeting that particular subtype of breast cancer - through a protein that is present in Triple Negative breast cancers called CDK7.

"There are drugs which can now be used to 'turn off' that protein, inhibiting tumour growth," he explains. "Clinical trials are taking place regarding these drugs."

* Immunotherapy

This new treatment is offering hope for forms of cancer such as melanoma and lung cancer which, historically, have been difficult to treat.

Research focusing on how cancers hide from our natural immune system has led to this entirely new form of therapy, explains Professor Gallagher.

"Drugs have recently been developed which can block that process and which expose tumour cells to the immune system. We have seen very dramatic responses to these immuno-oncology drugs in patients' melanoma or lung cancer, with even a subset - between 10pc and 30pc - experiencing what is akin to a 'cure'.

"While this new treatment option is not the universal panacea for cancer, it does offer significant hope for many cancer patients."

Patients should know that there is still a long way to go in terms of understanding what immunotherapy can actually do, cautions Dr Murphy.

"We've seen some stunning results in certain tumour types," he acknowledges, adding that Irish doctors can now avail of approved immunotherapy drugs for melanoma, lung cancer and kidney cancer. The treatment is being investigated with many other tumour types in ongoing clinical trials, he says, including investigations under his leadership at the Bon Secours Hospital in Cork.

"I have a number of clinical trials ongoing, among which are studies of immunotherapy in ovarian cancer and in Triple Negative breast cancer. We hope that immunotherapy will improve outcomes," he explains. However, Dr Murphy says, the big challenge is to identify the type of patient who will benefit from immunotherapy. Some patients can be overly optimistic about its reach.

"I have people coming with tumours that have not yet proven to be susceptible to immunotherapy. They are desperate to try it at huge expense to themselves and I counsel against that because without any evidence to support it, it is taking advantage of people's desperation."

* Improved Detection Techniques

It's not just treatment techniques which have improved, however. The oncology sector has seen huge improvements in detection techniques, explains Dr Murphy.

"Imaging and biopsy techniques are changing beyond all recognition. We've seen a revolution in imaging in the last 15 years. We now have Ultra High Definition CT scans and PET/CT scans and other highly sensitive imagery which are much better at detecting cancer more accurately in the body."

* Liquid Biopsy

Biopsy techniques are also undergoing radical changes, Dr Murphy reveals. Currently, a biopsy involves a core of tissue being removed, like an apple core, from a tumour - the problem is that the sample may not be representative of other areas of tumour in the body. However, that's about to change.

"We're now getting to a point where we will be able to investigate tumours by looking at tumour cells and DNA circulating in the bloodstream through a single blood test," says Dr Murphy.

He predicts that this technique, which is called liquid biopsy, is poised to change the way doctors diagnose and manage tumours.

"There has been a huge change in imaging in the last 15 years. Tumours evolve continually and with this technique it will be possible to carry out much better monitoring through a blood test which can be done regularly and with no great distress for the patient."

'Ireland needs more clinical trials'

• Clinical trials drive medical breakthroughs - they're crucial to the development of improved detection, diagnostic and treatment techniques, emphasises Professor Bryan Hennessy, consultant oncologist at Beaumont Hospital and clinical lead at Cancer Trials Ireland, the leading voluntary cancer research trials organisation in Ireland.

However, he says, clinical trials cannot be run without sufficient funding, staffing and resources. Professor Hennessy says Ireland needs more trials, more cancer patients willing to participate - and, crucially - more government funding.

"Our goal at Cancer Trials Ireland is to dramatically increase the number of trials here," he says, adding that he welcomes the National Cancer Strategy's objective of doubling to 6pc the number of Irish oncology patients on clinical trials by 2020.

Currently, just 3pc of all cancer patients, or about 6,000 people, are participating in clinical trials. In all there are 150 trials ongoing in 16 hospitals around the country, about 50pc of which are cancer trials.

Cancer Trials Ireland's long-term aim is to have 10pc of oncology patients on trials - which, Professor Hennessy points out, is the norm for many developed countries.

"The National Cancer Strategy dictates government policy - and that means we're likely to get more funding to increase the number of trials and get more new cancer drugs to more people with cancer," says Hennessy. "Cancer trials mean better treatment, longer survival. They also bring an economic benefit in terms of employment."

The big challenge for those involved in cancer trials, he emphasises, is getting sufficient funding. The Irish Cancer Society provides annual funding to the work of Cancer Trials Ireland. In 2017, for instance, this amounted to €500,000. But more is needed.

"The more funding we get, the more trials we run and the more treatments are developed," says Professor Hennessy. "Our funding was cut by 20pc by the Health Research Board a few years ago and we want that to, at least, be re-instated because it has had a significant negative impact on our ability to develop new trials and treatments.

He says that all advances in cancer treatment that are developed or will be developed emerge from cancer trials. "The will is there and the expertise is there but without funding we cannot build."

To run trials you need a special department in each hospital with qualified staff - research nurses, data managers and pharmacists.

"We're already struggling with what we have because of funding cuts," Professor Hennessy says.

● Details on all cancer trials open are available on cancertrials.ie

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