When too many conductors result in cellular discord and cancer
I'm looking for new treatment strategies for lung cancer. The issue with lung
cancer
, and really all cancers, is that what drives the disease in one patient may not be the same in the next patient and this can result in different responses to therapy. For example, some people will respond better to chemotherapy than others.
How is your project tackling this issue?
My project at
UCD
School of Biomolecular and Biomedical Science looks at a subset of lung cancer that typically doesn't respond well to current treatments.
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We want to find factors that are driving the cancer to grow in these subtypes so that we can create a treatment to go in and stop these drivers' activities and hopefully stop the disease in its tracks. In my project, the 'drivers' we are looking at are called long non-coding RNAs.
What are long non-coding RNAs?
Each cell in our body is a tiny, complex system made up of many components that have specific roles. Long non-coding RNAs can control this system by interacting directly with these cell components and guiding their activity.
Unfortunately, sometimes these controllers go awry and can guide the cell components incorrectly, which leads to the cell becoming unhealthy, and potentially cancerous. It is only in the last two decades that scientists have uncovered the true importance of long non-coding RNAs, so it is a very new and exciting field of research.
You recently won a speaking competition with a metaphor – tell us more.
I was lucky enough to take part in the UCD Engage competition, where PhD researchers come up with metaphorical way of explaining their projects in an engaging and accessible manner. My project funders, Breakthrough Cancer Research, introduced me to patient advocates Marian O'Mahony, Mary Neville and Siobh Siobhánes, and together we curated the metaphor of an orchestra.
How does it apply to your project?
In essence, a healthy cell is like a perfect symphony orchestra producing beautiful music. Imagine there are too many conductors, they are all shouting over each other and causing havoc, ultimately losing control, and what was once a harmony is now a screeching tragedy.
It's the same in the cell, if there are too many long non-coding RNAs, they can start to act a bit crazy and lose control of the cell components, and what was once a healthy cell can be driven to become an unhealthy, out-of-control, cancerous cell.
So the question is, if we can fire the excess conductors in the orchestra, or get rid of the extra long non-coding RNAs in the cell, can we bring back our perfect symphony or our healthy cell?
What do you hope the impact of your research will be?
If we find the long non-coding RNAs that are responsible for driving the cancer progression in our subset of lung cancer, we can create a treatment to target it. This means personalised treatments for many patients that currently don't have many options.
However, the process of drug discovery, testing and approval is extremely lengthy, meaning it will likely be some years before such a drug will be available clinically. My project is in essence a cog in the wheel of getting these treatments to patients, but each cog is important.
What do you like to do outside of research?
Sometimes the lab work can be quite stressful, so you need to have things outside the lab that you enjoy. For me, that's often spending time with family, heading to a pilates class or even doing a crossword – my grandad's love for The Irish Times crossword has been successfully passed down!
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'The idea of being around the kids with it still in my system does not sit well with me at all.' There is no getting away from the fact that cocaine is supplied by dangerous criminal networks but she tries not to think about where the drug comes from. 'I don't particularly want to know the details.' Sadhbh goes on to liken this to turning a blind eye to where cheap clothing may come from and the working conditions that may be involved. 'It's that kind of white privilege. That kind of cognitive dissonance. I don't think about it,' she says. 'My mum had always told me, even about hash or anything like that 'You know you're just funding criminals'. I don't ask my friend where she gets it. I don't particularly want to know. The fact that she's taking it alongside me makes me think that she's happy enough that it's okay stuff.' Harris of Coolmine says this is all part of cocaine being 'very socially acceptable'. 'If someone went in and injected heroin, I think people would be shocked to the core. It just would not be acceptable for people to use heroin in the workplace ... or socialising after the workplace. Whereas nobody's batting an eyelid to people using cocaine – until it becomes a problem.' 'For the majority of people that we see, their story is the same. It all started very recreational.' Harris says people buying cocaine are 'actually adding' to the wreckage of human lives and communities caused by criminal feuds. 'It mightn't be in your area, in Dalkey or Foxrock where they're having the feuds. But where do you think your cocaine is coming from?' BEN* 'My wife thought I was having an affair. I said, no, I'd been using coke every day. She had no idea' Ben, who is 51 and a father of three, had a disastrous experience with cocaine. When he started using the drug more than 20 years ago, he arrogantly believed he would never have a problem with it. 'Because I used it socially, and it was never something I felt I had to keep up the next morning. But it's a sneaky drug. It creeps up on you,' he says. 'I was 30 when I first used cocaine. It was very sparingly ... I took it once and then didn't take it for months. And then slowly, every time you're going out. It's just so accessible now.' 'It's not just a drug for young people. The pubs I drank in, there were 60-year-olds [on the drug]. Cocaine is from grannies down to teenagers.' 'It's a sneaky drug. It catches up on you.' Photograph: Paul Harris/Getty Ben says the drug is very easy to source. For those on a night out, the 'big thing' to observe is how people behave. 'You see people going in and out of the toilet ... You'll know it's going on. A thing that's being said all the time is, 'Have you got a number?' That usually means 'Have you got a number for somebody I can get?' At this point someone will usually offer a [phone] number.' Cocaine 'really took over' Ben's life during the Covid pandemic. 'I was on the Covid payment, I was at home so, 'Ah sure, I'll get a bag'. I'd end up using in the morning. I'd be ... at home painting the house, justifying it: 'I'm still doing things'.' Ben felt like he needed the cocaine 'to function' in life. 'It was every day, and then that evening. The bills were mounting up ... I wasn't paying bills. I was manipulating my kids to take the post out of the post box so my wife couldn't find them. The mortgage was going into arrears.' His wife knew nothing about his cocaine use. 'You become a master manipulator,' says Ben. 'It came to a head when we were driving one day. I was brought up with good values and morals, and I hated myself.' Ben's wife asked him, in the car, if he was having an affair. 'I couldn't wait to get it out of my mouth. I said, 'No. I've been using coke every day'. She had no idea.' 'I became so sneaky and devious, to get what I want, that nothing else mattered,' he says. 'She was devastated.' The marriage broke down. At 49 he moved back in with his parents. He had to explain to his wife that their mortgage was thousands of euro in arrears. He sought help initially 'to curry favour' with his wife, but admits he was still using cocaine on the bus to the treatment centre. Only later did he resolve to accept treatment for himself. He's been two years clean of cocaine and has reconciled with his wife. He knows he's lucky. 'I functioned for so long. Worked and used ... I functioned for so long, until it took over everything.' Harris of Coolmine says cocaine puts users on a 'gradual progression' to addiction. 'You could use cocaine for a very long time recreationally before it starts moving into problematic cocaine use,' she says. 'When I'm trying to get people to understand why would people use, when they know what the destruction is going to be, I say: 'That's where you're wrong.' 'They don't see themselves as that other person out there who has a drug problem. They see themselves as a person who's working, who can afford cocaine, who has a job, who has a family, and I use this because I feel good when I use it. It's the exact same kind of psychology as somebody going for a drink on a Friday after work.' Still, risk is never far away. Certain users drive while under the influence of the drug. Others admit to working on building sites after taking cocaine. The health and safety implications were clear but user's need for the drug was bigger. Cocaine doesn't only affect the person using it. Those who love the drug user are also deeply impacted. MUIREANN* 'My brother can get it anywhere ... He was at a show in Dublin last year. It was delivered to the matinee at lunchtime' Muireann's brother is a 47-year-old tradesman and father in a family with a middle-class background. He started 'dabbling' in his late twenties, she says. 'The usual, started smoking a bit of weed, then taking a few pills – and then to the cocaine,' she says. Her brother's marriage broke down because of his drug-taking. 'He's isolated himself from everybody,' she says. 'He can't be in social situations any more ... He just isolates himself away and stays in bed ... It's just awful, and there's nothing we can do.' Muireann says her brother is still using cocaine, which is delivered to his house. She tells her children, who are too young to understand the situation, that their uncle 'is not well'. They 'love him, because when he's okay, he's great fun'. Still, Muireann's husband doesn't want their children around her brother because of his cocaine habit. 'Obviously he [her husband] won't let them go in the car or anything. He drives high constantly.' Muireann says her brother can purchase cocaine easily. 'He gets it delivered to the house. He can get it delivered anywhere ... He was at a show in Dublin last year. It was delivered to the matinee at lunchtime, at the break,' she says. 'No problem. They can get it anywhere. I don't know how they do it. There's a world and it's just a text away.' Living in the same neighbourhood as her brother, she worries about safety. His car 'was smashed up outside the house', she says. 'He is a normal person. He's a gent. He's the most generous human, good-looking fellow, gorgeous, really successful man – and this has just taken every ounce of him from us. He's not the same. Even if he stopped today, I don't know would we ever get him back. I think his brain chemistry has changed that much now, he's gone into psychosis, where he thinks conspiracy theories.' Feeling helpless, she lives in fear of finding her brother dead. 'Nobody can help him until he reaches rock bottom, and I don't know what that looks like.' THE MEDIC 'Cocaine is known as the perfect heart-attack drug' Increasing cocaine use was reflected in data this week from the Rutland Centre, another drug treatment group. Rutland's annual report pointed to the increasing complexity of drug addiction with 77 per cent of residential clients presenting with two or more addictions. Cocaine featured heavily. Doctors see the effects in the emergency room. 'Ask any emergency physician and they will tell you, cocaine-associated chest pains is definitely something we see in Ireland, especially in the 30s and 40s,' says Dr Lisa Cunningham, consultant in emergency medicine at Mayo University Hospital. Dr Lisa Cunningham, consultant in emergency medicine at Mayo University Hospital She has seen an increase in presentations in this age group over the past 10 years but says some patients won't tell medics of their drug use. 'Some patients may disclose their cocaine use and some may not, even when directly asked. Especially with local hospitals, community, people knowing each other, patients may be reluctant to state it.' Cunningham says 'cocaine is known as the perfect heart-attack drug,' adding that 'even recreational use, or chronic cocaine use' has a huge effect on the heart. 'It leads to stiffer blood vessels, which causes high blood pressure in the body. It is known to alter the structure of the muscle of the heart – causing it to enlarge. This can lead to heart failure as the heart can't pump properly with an enlarged muscle.' Cocaine use can be associated with the build-up of plaque in the coronary arteries – the arteries supplying the heart muscle – leading to 'blockage' heart attacks. 'If the electrical stimulant of cocaine is too much on a heart, this can lead to cardiac arrest.' People in their 30s and 40s may already have 'traditional risk factors for heart disease beginning to appear: rising cholesterol, diabetes, sedentary lifestyle, high blood pressure, stress in life.' Adding cocaine to the equation can be 'like an accelerator to a fire,' she says. 'Cocaine tips the risk factors over the edge with monumental consequences. 'A common thing patients say to me is that they haven't had previous bad effects of cocaine, or their friends never had problems.' Cunningham says cocaine isn't made in a pharmaceutical laboratory, with healthcare professionals, quality assurance, safety and regulation checks. 'You literally do not know where this comes from in the world, nor do you know the motivation of people behind making it, besides financial gain at the expense of anyone's life,' she says. 'Every time you take cocaine, there is no regulated ingredient list, no idea what is in it, with no knowledge of what immediate effect it has on your health. That may be chest pain or it may be cardiac arrest. It does not matter if it's the first time or the fifth time. Every time you take cocaine ... the damage is being done, and there will be one time that potentially the heart will not be able to cope.' *Names have been changed
