A ‘stepping stone’ on the path towards a potential treatment for one of the hardest-to-treat forms of breast cancer – that’s how Kerry native Dr Catríona Dowling characterises the exciting discovery she, and the research team she led, has just made.
ailed in the media as a ‘breakthrough’ in our understanding of ‘triple negative’ breast cancer, the discovery was last week set out in research journal Science Advances in a paper on which the Ardfert woman was lead author.
Affecting around one in every eight women diagnosed, triple-negative breast cancer is more common in younger women and sufferers are more likely to develop resistance to chemotherapy; which is used in the treatment of 70 per cent of triple-negative cases.
What Dr Catríona, a lecturer in Biomedical Sciences at UL’s School of Medicine, and her colleagues discovered were the curious properties of a certain molecule; one which selectively killed the triple-negative cancer cells while leaving healthy cells unharmed.
And in applying the molecule to the cancer cells in the course of the long study, conducted at RCSI University of Medicine and Health Sciences in Dublin, they also figured out exactly what it is that makes the cancer cells effectively tick.
“It’s certainly like a stepping stone I guess towards a treatment, there’s still a lot of work to be done of course as we still have to now to develop that small molecule into a drug,” Dr Catríona told The Kerryman this week.
“What we were looking for was some compound that would cause harm to this very hard-to-treat cancer without harming other cells and eventually hit on this specific molecule, known as BAS-2, through collaborating on the screening of hundreds of compounds already synthesised with colleagues at the Dana-Farber Cancer Institute in Harvard.”
“It’s a small molecule that we knew actually harms breast cancer cells but without fully understanding it we had no idea of its function. So we had to figure out what exactly it was doing in these breast cancer cells and that led us to discover that it actually inhibited a particular enzyme called HDAC6, a protein basically,” Dr Catríona said.
Then came the really interesting breakthrough. “We then figured out, and this is very novel in the field of research, that this protein alters the energy of cancer cells. We know cancer cells use a lot of energy and that’s what keeps them alive and causes tumours to develop.”
It was known that the protein was important in keeping the cancer cells alive, but the Kerry woman and her team conclusively cracked its enigma. The BAS-2 molecule essentially deactivates, or inhibits, the HDAC6 protein, stopping the cancer cell metabolism dead in its tracks – without harming other healthy cells.
“There have been other drugs that have tried in clinical trials targeting this protein, but the difference with our compound is that it’s very specific to this and doesn’t have any other off-target effects, unlike others seen in clincial trials.” Now, Dr Catríona is continuing the research journey through her own laboratory in UL where she hopes to play a part in even developing treatment for lung cancer. Until Covid exploded she had been working in New York under one of the top lung cancer researchers in the world – leaving to take up her current position in UL just as the Big Apple became the global epicentre of the pandemic.
“For me, cancer research is definitely where I want to be, and I would love to be able to say at the end of my career that I have made a difference to the lives of some cancer patients and their families. And if that takes 20 or 30 years that doesn’t matter, you always have to see the end goal and persevere…I guess these kind of breakthroughs turn on the lights as you go along.” The development of the drug from the current research will be carried out under Dr Tríona Ní Chonghaile, RCSI lecturer in physiology and medical physics, who supervised the BAS-2 research.
Reaction to the study, in medicine and the media, has been effusive – as at home in Ardfert where her family could not be more proud. There have been a number of proud moments of late: not least when her dad Pat made his first trip abroad, accompanied by her sister Maria, to watch Dr Catríona running the New York City Marathon in November 2019. Her mom Ita, who was unwell at the time and couldn’t travel, cheered on from home in the company of Catríona’s brother John (of Tralee Warriors fame).