Interview with Christian Frezza

We asked Christian Frezza about the history of cancer metabolism and latest advances in the field.

Christian Frezza is currently an MRC Group Leader at the MRC Cancer Unit, University of Cambridge. His research focuses on understanding the metabolic transformation of cancer cells.

Christian will be co-chairing the third in our series of Metabolism and Cancer meetings, to be held in September this year. We caught up with Christian to ask a few questions about the field of cancer metabolism, and find out his thoughts on the upcoming Cancer and Metabolism 2015 meeting.

Abcam: Could you briefly introduce us to why changes in metabolism are important for tumor growth?

CF: Cancer cells proliferate at a very fast rate compared to normal differentiated cells and frequently live under harsh environmental conditions. For these reasons, cancer cells need to rewire their metabolism to fulfill the increased energy requirements of fast proliferation.

Metabolism of cancer cells by and large is not different from that of any other normal proliferating cell in that they all need nutrients to proliferate and survive. However, some of them activate specific metabolic pathways, making them unique metabolic machines.

It is worth mentioning that the actual idea that cancer cells have different metabolism as compared to normal cells is not new, but it took more than fifty years to convince scientists that this aspect of cancer cell transformation is relevant and that it could offer important pharmacological targets.

Christian Frezza (second from left) with his lab group. From left to right: Vinny Zecchini, Christian, Marco Sciacovelli, Alizee Vercauteren, Sofia Costa, Isaac Johnson and Edoardo Gaude.

Abcam: How did you come to focus on this research area?

CF: I started my scientific career as a medicinal chemist at the University of Padova. Here, I developed anticancer drugs that would target mitochondria upon illumination with UV light. This experience offered my first encounter with mitochondria and, since then, I have been in love with these organelles.

In fact, I decided to do my PhD in mitochondrial physiology in the laboratory of Luca Scorrano. Here I looked at mitochondrial metabolism from a slightly different point of view, looking at specific bioenergetic features of mitochondria.

In 2006 Eyal Gottlieb came to Padova where I was doing my PhD and presented some of his recent work on succinate as a metabolite capable of driving oncogenic processes. This discovery was really groundbreaking for me; it opened up a new way of thinking, a new paradigm where mitochondrial dysfunction—which I was studying from the very core—could play a role in tumor formation.

As a medicinal chemist with a keen interest in translational medicine, I decided that Eyal’s lab would have been the perfect place to apply my knowledge of mitochondrial physiology to one of the most relevant human diseases, cancer. I therefore decided to join the laboratory of Eyal Gottlieb for a postdoc in 2008.

Here, I started to work on fumarate hydratase, a mitochondrial tumor suppressor involved in a very aggressive type of kidney cancer. This work enabled me to exploit my expertise in medicinal chemistry and in mitochondrial biochemistry and apply it to cancer.

Abcam: Our last metabolism and cancer meeting was held  in 2013, what has changed in the field since then?

CF:  Quite a lot! Looking at the abstract books from 2010 and 2013, you can actually see what has changed. 2010 was still the beginning of the field. We already had some very good speakers coming, but the community was very small and the mainstream scientific community was still skeptical. I think this was a descriptive age for metabolism.

From 2010 to 2013 we witnessed a massive explosion of the field and scientists started to take metabolism more seriously, including in the scientific pipeline state-of-the-art technologies, from metabolomics to computational biology and epigenetics.

I think we are now in a new phase of the field, beyond the simple characterization of the metabolic transformation of cancer. Indeed, we are now trying to understand whether and how altered metabolism can promote tumorigenesis.

A new paradigm is emerging whereby small molecule metabolites accumulated as a consequence of metabolic dysregulation can alter the fate of the cell and predispose them to tumorigenesis; this is quite a change of mindset. These oncometabolites are now in the spotlight of the field and I am sure we will hear a lot about them during the 2015 meeting.

Abcam: You refer to the beginning of the cancer metabolism field as being just a few years ago. Hadn't the field begun many years ago with Warburg's discoveries?

CF: Yes you are correct: our current scientific endeavor stands on the shoulders of giants, and one of those giants was actually Otto Warburg.

Warburg started his work at the beginning of the 20th Century. After developing very elegant models of cancer and seminal tools to assess cellular metabolism, Warburg came to the conclusion that on the origin of cancer cells there is a defect in mitochondrial respiration.

After almost a century from these discoveries, we know that this bold statement holds some truth. Not only it was found that all cancers exhibit, to varying extent, a metabolic reprogramming, but it was also demonstrated that some of the major oncogenes and tumor suppressors actually play a direct role in metabolism.

Although it was initially believed that altered metabolism was a simple epiphenomenon of the genetic transformation of cancer cells, there is now evidence that altered metabolism can actually drive some of these genetic changes. In an upside-down view of cancer, oncogenic mutations can be seen as means, rather than causes, to the metabolic reprogramming of cancer required to sustain accelerated growth and proliferation.

Abcam: Are there any particular speakers that you are especially looking forward to hearing from at the meeting?

CF: I am looking forward to hearing from all of them because they are all excellent, outstanding speakers that have contributed to the field so dramatically in the last two years. I think what I am waiting for is to see the switch in mindset that I anticipated will happen, and I want to see the fruit of these five years of work in the field, and how it has contributed to changing the way we approach cancer.

The third Abcam Metabolism and Cancer meeting will be held in Cambridge, UK on September 28–30, 2015. The full line up has now been announced. Find out more or register.