In Teenage and Young Adult Cancer Awareness Month, we are celebrating the scientists carrying out innovative research to help improve outcomes — including Dr Olivier Pardo at Imperial College London.
In our interview, Dr Pardo shares how a coffee with Jeff Bezos could support cancer research and crushes common misconceptions about the "eureka moment."
Please can you give us an overview of your current research project?
The problem with osteosarcoma is that when the cancer is restricted to the primary location, it is most accessible for therapeutic intervention such as surgery or chemotherapy. But once the cells start travelling though the body to other areas (distant metastasis), this is where we hit problems in terms of curing patients.
Most cases of death in cancer are linked to the development of distant metastasis. One of the most important steps in tumour cells forming distant metastasis is they need to enter the bloodstream to reach distant organs.
Once the cells enter the blood, they suffer tremendous stress because of huge changes in blood pressure. They go through the heart where pressure is incredibly high. We always assume this is a bad thing for cancer cells. This is true, in that most cells will die due to this stress.
However, a subpopulation of cells an adapt to stress. This adaptation makes them more aggressive, and it is something that's very understudied. We want to understand what happens to these cells in response to mechanical stress that enables them to adapt and become more aggressive. From this, we hope to develop new treatments that prevent the survival of cancer cells in the bloodstream, changing their aggressive nature and making them more responsive to treatment.
What motivated you to study how osteosarcoma cells travel through the bloodstream?
Four years ago, I met a young man aged 17 who had his leg amputated due to osteosarcoma. At that point, he had a good chance of being cured — he was so full of life and hope for the future.
Unfortunately, he later developed lung metastasis and just one year later, he died. This really shocked me because for someone that young, death shouldn't be on the cards.
We know that the difference between life and death in osteosarcoma is the development of metastasis, with lung metastasis being one of the main contributors. It really made me think that if we could address that problem, we could potentially increase the number of patients being cured.
In the case of lung cancer, most of the time we fail to cure the original tumour, so even if metastasis was curable the patient would still often die. But in osteosarcoma, we should be able to get around that through surgery, so the main issue is metastatic disease which we are hoping to address in this study.
What innovative methods or techniques do you use in your research, and why are they effective for your work?
Scientists in the past have tried to answer how osteosarcoma travels through the bloodstream by using microfluidic devices. These are engineered simulation systems in which cells can circulate as they would do in the blood.
They tried to discover what changes in cells as they circulate, but unfortunately their efforts were lacking in two respects. Firstly, the circulation they tried to reproduce was not physiological. It involved constant pressure, whereas we know when cells travel through the blood, they experience low pressure to very high-pressure environments and back to low pressure again.
It is the variation of pressure that induces most of the stress, just not constant pressure. The microfluidic device that we develop will reproduce these variations, so it will better mimic the journey of a cell through the body. For example, a small blood vessel where the pressure is low, to the heart where pressure is extremely high. We also look to mimic the time that cells spend in the different areas to produce a journey that's more representative.
Previous studies assumed that after a while in circulation, the cells were stressed. This is because they had no way of monitoring at what point the stress really started. We will look to address this by using a system that enables us to visualise when the cancer cells become stressed, so we can concentrate our analysis on cells only when we know they are in the right state.
What sparked your interest in the field of research?
I don't think I have ever wanted to be anything but a scientist! The first time someone asked me what I wanted to be when I grew up, I was six years old, and I said that I wanted to be a scientist. The idea that you're looking for something that's never been seen before has always excited me.
If you could have coffee with a famous scientist, who would it be and what would you ask them?
I've been very fortunate in that I've already met and worked with many brilliant, famous scientists. I would rather have a coffee with someone who works on the data analytics side — people at Microsoft, Google... perhaps Jeff Bezos at Amazon to discuss how we could use artificial intelligence (AI) and data analysis to help cancer research more than we do currently.
The problem is that we've accumulated so much data, especially in the last twenty years. It is very difficult for us to keep track not only of what other scientists are doing, but also our own data because it is so extensive.
I think that's where AI is going to make a big difference. Not in replacing us, but in helping us focus onto what is important and make connections.
Is there a research myth or stereotype that you would like to bust once and for all?
The idea that pressing a button on a machine spits out a result that changes everything immediately. It never happens like that... well, at least it has never happened to me!
We think that all experiments lead to results, but often the results are negative... you go from a no to a no until you find a yes. Ultimately, it's a process of elimination most of the time.
The simple button that you see in a movie turns out to be four years of experiments. Nothing is that fast or that easy unfortunately.
What is your favourite part of the research process?
All of it! From coming up with ideas and thinking 'I wonder if...' to doing the experiment, seeing something new, and integrating it with what you already know.
Something that I think is an underrated part is presenting your findings to others and exchanging ideas. I think the entire journey is quite exciting.
Is there a book, podcast or show that keeps you inspired?
There is a book I think about when I need an uplift. It is called The Pleasure of Finding Things Out by Richard Feynman, who was a famous quantum physicist.
During his PhD, Richard was exploring a new approach to quantum mechanics. He was an amazingly funny individual who has written a string of books full of wonderful humour. They are not scientific, but reflect on moments of his journey as a scientist with a focus on the funny side. I would highly recommend his writing to anyone.
Have you faced any unexpected setbacks or failures, and how did you learn from them?
Every day! Another myth about science is that you succeed a little bit every day. It is generally the opposite: you fail a little bit every day, but learning from those failures is what's important.
There are so many options and different ways a project can go. Each time one door closes, you decrease the number of options and are centering on the one that will give you an answer.
Do you have a message for osteosarcoma patients going through treatment?
As scientists, we know the journey is long. We appreciate that patients will wonder what we are doing all day and why we haven't found a cure yet.
I would like patients to know that we are working incredibly hard to try and make a difference. The process is so difficult, and we feel like failures all the time because we can't deliver what we want to deliver.
However, we will get up and try again until we reach the point where we've found something and can make a difference. We will get there in the end, because there's no way we can allow this disease to win. That's not an option.
Learn more about Dr Pardo's study co-funded by the Bone Cancer Research Trust and CCLG: The Children and Young People's Cancer Association, below: