The “Cancer and Metabolism” conference series started in 2010 with the simple idea to bring together the community of scientists investigating metabolic transformations in cancer. Over the years, the meetings have become a forum where a growing number of researchers can discuss the latest research on cancer metabolism and explore therapeutic approaches targeting cancer-specific metabolic pathways.
There were lots of discussions after the talks. And I think that was helpful for moving the field forward.Dr. Eileen White, Rutgers Cancer Institute of New Jersey, USA
The 2022 edition took place at the Francis Crick Institute, London, UK. We talked to Oliver Maddocks, Professor at the University of Glasgow, UK, and one of the scientific organizers of “Cancer & Metabolism 2022”. He shared with us his thoughts about the major themes in this year’s edition, panel discussion insights, and the big challenges in the cancer metabolism field.
How did you find this year’s Cancer and metabolism?
“This was a fantastic meeting with a nice, focused feel. It’s great for the community focusing on cancer metabolism to come together and have these hardcore cancer metabolism meetings. I was lucky enough to attend the first meeting in Edinburgh, taking on the role of a poster judge. That was possibly my first ever meeting in cancer metabolism once I’d started at the Beatson as a post-doc. That was a great experience to be involved in these meetings right from when I started working in the field. It’s been nice to have presented in prior ones and to be involved with organizing this one, taking over from the fantastic Christian Frezza.”
What were the major themes this year across the talks?
“Formate metabolism came out pretty strong. Talks from several speakers featured formate, including Karen Vousden, Marcia Haigis, Johannes Meiser and Elisabeth Letellier. So if you wanted to pick metabolite of the meeting, this geeky honor probably goes to formate.
The panel discussion was interesting, and some themes came out of that. One theme was the requirement for good selection and stratification markers for developing therapeutic strategies. It’s essential to know what patient population you’re targeting in terms of tumor type and mutational or gene expression status, so having good markers for stratification should be key to developing new strategies.
Another strong theme was using diet and what we currently consider non-canonical ways to corral metabolism into a way that can be vulnerable to other therapeutics. Several talks referenced diet and using the diet in combination with therapeutic agents.”
You’ve touched on it already, but could you summarize the key ideas and conversations in the panel discussion?
There were four themes in the panel discussion, and I briefly mentioned two of them earlier. The first theme was the biomarkers and selection markers. We can’t develop generic interventions to throw at a broad population of cancer patients and hold them to succeed because there will always be people who respond well and those who don’t. If you combine all of those people, you won’t get power in your data to be able to validate an intervention. So you have to understand the mechanism really well, which resonates with this type of meeting. These meetings and this community are essential for doing that rigorous science: molecular biology, molecular genetics, and the real mechanistic hard work behind pharmaceutical and dietary interventions. This science will then allow us to choose the right patients for interventions and have a set of tools to go into the clinic that enables us to check those markers, whether it’s sequencing, immunohistochemistry, or detecting some metabolic biomarker in the blood.
The second theme was the idea of being able to use diet because metabolism is very plastic and adaptable. If you want to target it with a small molecule, say, a moving target, and you throw that small molecule in, metabolism just adapts and changes. Suppose you can use diet to prevent that adaptation and pin down the broader metabolic rules by using diet. In that case, when you put a therapeutic in the diet, metabolism can’t escape so easily from your therapeutic because it’s being constrained in place by the diet rules.
Another theme was the idea to target not just tumor metabolism specifically, i.e., the metabolic pathways in the tumor, but systemic metabolism that surrounds the tumor. That’s really important in thinking about how we can get responses to small molecules, more conventional therapeutics, and radiotherapy. Systemic metabolism can also play a role here, and we can improve therapeutics by controlling systemic metabolism and side effects.
The last interesting theme is that developing a field like cancer metabolism can take time. Everyone gets very excited at the start. But when a few targets fail in the clinical trials, everyone gets disappointed. The message shared during the panel discussion is that it takes time to go through those peaks and troughs and reach a stage where you truly know enough about how to tackle this problem for therapy to work. The parallel was drawn with cell cycle and CDK inhibitors, which are now successfully used in the clinic but have gone through 25 years of getting to grips with understanding the cell cycle before being able to drug it successfully. So we need patience and perseverance to weather these peaks and troughs of enthusiasm and keep doing the basic science to finally reach a point, maybe after 25 years, where you start making genuine progress in the clinic.
To summarize, I think it was an exciting panel discussion. We had some great panelists, and I think the discussion could have continued further.
In your opinion, what are the biggest challenges that researchers are facing or will face in the area of cancer metabolism?
I think the same challenge that anything new faces: getting the message across to all the involved stakeholders that this can work and the science is robust. In my opinion, many oncologists and patients already have this mindset, but we need to expand it to the broadest set of people possible.
For example, many oncologists strongly believe metabolism is underplayed and underused in cancer treatment. These oncologists require no persuading, but they need good tools and robust clinical trials that they can put patients into. There are already groups of patients willing to go on those kinds of interventions, and they will be pioneering and leading the way as patients to help develop these therapies further. I think overcoming the challenge of a more generalized acceptance comes through embracing those pioneering oncologists and patients and allowing them rigorous clinical trials.
What advice would you give to young researchers in the field? How do they get past those restraints?
Do what you enjoy. Work hard. Find good people to work with. Try to think of the most relevant clinical problems and how basic research could push our understanding forward.
We hope you enjoyed catching up on the latest cancer metabolism insights with Oliver Maddocks. To give you even more insight into this year’s meeting, we’ve also recorded short videos with two of our speakers. Hear our keynote speaker, Prof Eileen White from Rutgers Cancer Institute of New Jersey, USA, talking about her research journey and where she sees the field going in the next decade.
Watch this short video of Dr George Poulogiannis, a team leader at the Institute of Cancer Research, UK, who spoke about the role of diet in enhancing therapy.