Cancer research: the next step

As well as providing services for sufferers, the Irish Cancer Society is aiming for excellence in research, writes DICK AHLSTROM, Science Editor

TOMORROW is Daffodil Day, the Irish Cancer Society’s main annual fundraising event. The society receives no State subvention and yet last year it responded to about 25,500 callers on its help lines and invested €3.8 million in pioneering cancer research.

The society has a very clear view of what it wants to achieve with the funding, 95 per cent of which comes from voluntary donations of €10 or less, says its first head of research, Prof John Fitzpatrick. “This is a very important and strategic thing for us.”

It supports a mix of centres and cancer types but the idea is to create a cadre of young and dynamic cancer researchers, he says. The society funds students studying cancer as part of their PhD research but also post doctoral students trying to establish their research credentials.

“We want to get them early and get them on their way with their careers,” Prof Fitzpatrick says. “We also want them to do research in Ireland.” They will become the next generation of senior researchers working on cancer and related diseases.

The society has raised between €17m and €20m annually over the past few years, says its research manager, Dr Sinead Walsh. “We have managed to stay quite steady during the recession.” It invested €3.8 million in research, €3.1 million of this in new grants in 2011, she says. Other funds pay for the help lines, advocacy, many other services and of course the “Daffodil nurses”, the oncology specialists that are highlighted on Daffodil Day.

The research money is carefully targeted she explains. “We are trying to build competency in cancer research, and it is used to expand the pool of cancer researchers in Ireland.”

Giving tumours the one-two with yoghurt bacteria

BOXERS OFTEN win fights with a one-two punch and the same approach may work for cancer treatments. A researcher in Cork is working on a two-step attack on tumours based on the use of a common dairy bacteria found in probiotic yoghurts.

Dr Michelle Cronin is an Irish Cancer Society Research Fellow funded over the next three years in University College Cork’s Cancer Research Centre. She is part of the gene therapy group and works with mentor Dr Mark Tangney. The Cork group has already shown that eating or injecting harmless bifidobacteria enables them to travel around the body. It so happens though that the anaerobic conditions inside solid tumours – as occurs in breast, ovarian, prostate and oesophageal cancers – provide ideal conditions for the bacteria, Cronin says.

They lodge and multiply readily in the centre of the tumour but don’t invade cells or cause tissue damage. One approach involves adding a gene to the bacteria to make them produce cancer-killing substances, but a collaboration with Dr John Bell at the Ottawa Hospital Research Institute in Canada has opened up a new approach.

His group works with “oncolytic viruses” – viruses that attack cancer cells but are harmless to healthy tissue. Unfortunately the immune system clears them out. But if probiotic bacteria are first encouraged to grow they release a protein called B18R that helps the viruses to survive longer in the tumour. They invade the cancer cells to trigger natural cell death.

Centrosomes are central for pivotal prostate study

WHEN CELLS divide they do a carefully choreographed two-step, with one cell changing into two. Cancer researchers plan to interfere with this ballet in the hopes of developing new therapies.

Irish Cancer Society researcher Prof Ciaran Morrison is studying this approach in prostate cancer, among the most common cancers in Irish men. Based in the Centre for Chromosome Biology in the School of Natural Sciences, he plans to target the “centrosome”, a structure that controls the process.

Cells have two centrosomes, he says.

“They move away from each other when the cells divide. If you mess around with the cell you can end up getting more than two centrosomes.”

This disturbs cell division, slowing it or stopping it all together.

He and his group are studying whether prostate cancer cells are more easily killed if they are forced to produce extra centrosomes. Using this approach the patient would first receive some form of chemotherapy to interfere with the genes that hold the centrosomes together, or perhaps a drug could do this.

Radiation is a common therapy for prostate cancer, but Morrison wants to see whether it is more effective at killing the tumour when its cells have extra centrosomes.

The work is in its early days and the Cancer Society funding will help keep a PhD student involved in research for three years. They will study centrosome abnormalities in detail and how this changes how the cell survives.

They will also look at why cells form incorrect numbers of centrosomes.

Rising reflux acid and the risk to the oesophagus

RESEARCHERS AT St James’s Hospital in Dublin are looking for better ways to predict those most at risk of developing oesophageal cancer. Their research could deliver earlier warning and better survival for this difficult form of the disease.

“Cancer in the lower part of the oesophagus has become one of the fastest-growing cancers in Ireland,” said Irish Cancer Society Research Scholar Dr Naoimh O’Farrell. The oesophagus is the food pipe which connects the mouth and stomach.

A medical doctor and surgical trainee, O’Farrell is also working towards a research PhD with a study of patients with “Barrett’s oesophagus”, a pre-malignant condition that increases cancer risk by 30 to 40 per cent. It occurs when these tissues are damaged by stomach acid that can rise up into the lower oesophagus. Her surgical and research roles mean she works with two group leaders, Prof John Reynolds, professor of surgery at Trinity College Dublin and St James’s and Dr Jacintha O’Sullivan, whose group has made important findings about Barrett’s oesophagus.

“The goal is to be able to identity patients at risk of Barrett’s oesophagus, but we also want to see if we can study the progression of the condition,” Dr O’Farrell says.

St James’s is a leading centre for the study of this cancer and runs a tissue biobank and registry funded by the Oesophageal Cancer Fund. O’Farrell and her colleagues are doing detailed DNA studies looking for random mutations that arise after exposure to acid reflux. This could provide biomarkers that identify patients at greatest risk of developing cancer.

Restoring order to cells may help block breast cancer

THE DELICATE interplay between two biochemicals inside the cell may be the deciding factor on whether a woman gets breast cancer. A research team at the University of Limerick is studying the complex interactions between these two proteins in the hope of blocking the onset of the disease.

Maeve Kiely is a PhD student funded by the Irish Cancer Society. She and her research leader, Dr Patrick Kiely (no relation), work in the Department of Life Sciences at UL within the Laboratory of Cellular and Molecular Biology.

She is growing breast cancer cells in the lab to study in detail how two proteins, RACK1 and PP2A work together in these cells. PP2A is a tumour suppressor gene, Kiely explains. RACK1 controls the movement of other proteins inside the cell and also binds directly to PP2A. If the relationship between the two goes wrong the result can be breast cancer, she says. “We are trying to understand what happens when there is a breakdown in the relationship between PP2A and RACK1.”

The cell cultures will help her to do this, allowing her to “knock out” one of the two genes for these proteins to see what happens to the cultured cell. It will provide hard details about their interaction and whether this could offer a way to block the onset of this disease by renewing the cordial relationship between the tumour suppressor and RACK1, the cellular traffic cop.

“I believe that if we work hard to understand this breakdown, we will be able to design ways of restoring the order and peace in the cell again, allowing all the proteins to act like normal,” she says.