A small research team in Belfast has uncovered a significant clue to unlocking the mysteries of breast and ovarian cancer, writes Dan Keenan
A team of specialists at Queen's University Cancer Research Centre in Belfast are a step closer to understanding why a fault in a single gene gives some women a significantly higher chance of developing breast cancer.
That step comes in the form of their latest research, which suggests that, in healthy women, a gene known as BRCA1 helps the body look out for cells which may be cancerous and forces them to self-destruct. However, when BRCA1 is faulty, this surveillance system "misses" cancer cells, allowing a tumour to develop.
Dr Paul Harkin leads the research group, which is now focused on defining the precise function of the BRCA1 gene. This gene is defective in about half of women who are genetically prone to developing breast and ovarian cancer at some stage in their lives.
It was already known that BRCA1 is important in repairing gene damage which can lead to cancer, but crucial new work by Dr Harkin's team suggests that BRCA1 is also involved in spotting damaged cells.
"The BRCA1 gene has multiple roles," Dr Harkin told The Irish Times. "It is well-known for playing a very defined role in repair of damage to DNA."
The team is trying to understand exactly how defects in this gene lead to the development of cancer and how it might use this information to develop new treatments for these patients. Recently, the researchers reported a novel new role for this gene in helping the immune system to track down and kill breast cancer cells.
"What we have shown is that it can also induce a cell death signal in cancer cells, and especially cancer cells that have been exposed to a molecule called interferon gamma".
The team discovered that this death signal is blocked in cancer cells which have a defect in BRCA1. They demonstrated that putting BRCA1 back into these cells could reactivate the death signal, leading to destruction of the cell by interferon gamma. It is hoped that this information can be used to develop new treatments for breast cancer patients in the future.
"In those breast cancer cells where BRCA1 is missing or mutated, then that cell death signal doesn't get transmitted right into the cell. So the cancer gets a chance to evade the immune system," Dr Harkin said.
Scientists believe that understanding the role of BRCA1 is vital to finding ways of preventing cancer. Women who have a fault in the gene have between a 65 and an 85 per cent chance of developing the disease at some point in their lives, and they have an increased risk of ovarian cancer.
Asked if the faulty BRCA1 can be repaired, he explained: "There are gene therapy approaches, the idea being that you take patients who have a defect of this gene and you reintroduce a normal copy of the gene. Now, that is still at a developmental stage. There are all sorts of issues associated with that. Principally, can you effectively target the gene to the tumour cells? Numerous other researchers are working to resolve those issues."
He said that the discoveries made in Belfast "definitely have the potential to lead to new treatment", but he added: "The challenge is - can we find another way round the pathway? Can we put something into those cells that will substitute for BRCA1. That's what we are looking into."
He added that they were still trying to uncover what it is that makes these two organs cancer-prone. Discovery of an answer to that could point the way to new forms of treatment.
Dr Harkin emphasised that people tended to refer to cancer in the singular, as if it was only a single disorder. "But cancer covers a range of very diverse disorders. The strange thing is that, for families who have inherited mutations of this gene, every cell in their bodies has a mutated copy of BRCA1, yet they only develop breast or ovarian cancer. One of the big issues is why do you get that specificity?"
Prof Patrick Johnston, director of the Cancer Research Centre, says that the results were beginning to shed light on why some women have such a high risk of developing breast cancer.
The researchers used a cutting-edge technique called microarray technology. One of the authors of the study, Ms Heather Andrews, explains: "Our results showed that BRCA1 interacts with a specific part of the body's immune system, a chemical called interferon gamma. This chemical acts as the eyes and ears of the immune system, scouring the body for diseased cells. The immune system then forces these cells to self-destruct, preventing the growth of a tumour."
In cells from breast tumours where the BRCA1 gene is dysfunctional the researchers discovered that this interferon gamma surveillance seems to break down. However, by adding a healthy copy of the BRCA1 gene, they were able to restore the surveillance system.
Cancer Research Northern Ireland's chief executive, Sir Paul Nurse, said: "In most cases, breast cancer is caused by damage to genes which builds up over a lifetime, but a percentage of people are born with a high risk of the disease. If we are going to help these people and know more about the disease, we need to understand why one faulty gene can make such a big difference. Dr Harkin and his team are bringing us closer to this aim."