In recent years, the neuronal component of the cancer microenvironment and the metabolic plasticity of cancer cells have become increasingly recognised as essential for cancer progression. Dr Simon Grelet and Dr Gustavo Ayala are two key researchers who work at the interface of cancer neuroscience and cancer metabolism, investigating metabolic reprogramming as a consequence of tumour innervation. In this episode, we will discuss their research on neuron- cancer cell transfer of mitochondria.
Read more about the publication here.
Our guests in this episode
- Dr. Simon Grelet, Mitchell Cancer Institute, University of South Alabama
- Dr. Gustavo Ayala, Physician Scientist at University of Texas
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Our host is Dr. Alexandra Boitor, EACR Scientific Manager.
Episode transcript
Alexandra: Hi everyone and welcome to Episode 32 of The Cancer Researcher podcast, brought to you by the European Association for Cancer Research. I’m your host, Dr. Alexandra Boitor, Scientific Manager at the EACR, and in this episode, we will discuss some research featured in the EACR’s Highlights in Cancer Research.
To set the stage for today’s conversation, I start by saying that many cancers are innervated and, in recent years, the neuronal component of the cancer microenvironment has received increasing attention. At the same time, the metabolic plasticity of cancer cells is becoming increasingly recognised as essential for cancer progression.
Dr. Simon Grelet from the Mitchell Cancer Institute, University of South Alabama, and Dr. Gustavo Ayala, Physician Scientist at the University of Texas, are two of the scientists that lead research at the border of these two research fields – cancer neuroscience and cancer metabolism. More exactly, they are looking into metabolic reprogramming as a consequence of tumour innervation.
Previous studies from their groups demonstrated how cancer innervation and cancer cell plasticity are intimately linked. More recent research from their lab is looking into the cell-cell transfer of mitochondria, which has recently become a subject of investigation as it has crucial functions in health and disease.
In this episode, we will discuss their paper entitled Nerve to Cancer Transfer of Mitochondria During Cancer Metastasis, published in Nature last year, and featured in the EACR Highlights in Cancer Research. Let’s dive into today’s topic.
Hello Simon and Gustavo, and thank you so much for allowing us to glimpse into your research.
Gustavo: Hi. It’s a pleasure being here.
Simon: Thank you. Thank you for the invite. I’m glad to be here too.
Alexandra: One of your recent papers is looking at the impact that tumour innervation has on the metabolic plasticity of cancer cells and subsequently on the aggressiveness of breast cancer. What made you direct your attention to the intersection of cancer neuroscience, and cancer metabolism?
Simon: I think that’s such a long story and Gustavo may want to start because he was a pioneer in this field.
Gustavo: Sure. I mean it’s 27 years ago. We did our first paper, and that paper just told us that cancer nerves played with each other, talked with each other, were good for each other. They made each other grow more. And then we found out that if you cut the nerves, tumours don’t form. And we started to find a trans-species signature of nerve effect, and that was alterations in metabolism. Essentially, if nerves are not there, cancer follows the Warburg effect. But if nerves are there, they become metabolically efficient. You cut nerves, they go back to being glycolytic.
And so for the longest time we looked at how this happened and we really couldn’t find a transcriptomic profile that would justify that. And then I met Simon, take it from there.
Simon: So basically, yeah, I would say, I started to study cancer innervation way after Gustavo, actually. But it was because of Gustavo, because years ago I was studying cancer plasticity. So most of my work revolved around the cancer progression and especially focusing on cancer metastasis, because that’s related to cancer associated mortality. And few years ago, I was studying cancer plasticity and figured looking at some transcriptome data sets, that cancer cells actually express neuron related molecules. They express molecules that are supposed to be expressed in neurons, typically that you can find in the brain, Axon guidance molecules. And I was studying cancer cells on the Petri dish, not even on a mouse, and that’s where I started to scratch my head and that’s where I stepped in the field of cancer innervation, and looking at what had been done in the field.
Actually when I started there was not many papers. But there was some of these seminal papers from Gustavo about Axon guidance molecules that are secreted by prostate cancer cells and that attract neurons into the tumour bed (https://doi.org/10.1158/1078-0432.CCR-08-1164; https://doi.org/10.26508/lsa.202101261; https://doi.org/10.3390/cancers15072026).
And that’s where I really started to think about, there are neurons in cancer. I never thought about that before. I was thinking about obviously the immune cells, the fibroblasts, but I never thought about neurons. And still, when I talk about my work right now, I meet people that have the same reaction that I got few years ago about neurons in cancer, but now it’s more and more accepted.
So that’s how I stepped in the field. And when I established my research laboratory, I entirely focused in this topic because I think that’s a very important and uncharted territory in cancer research.
Alexandra: As you have highlighted Simon, this is a new field of research. I mean, cancer neuroscience is a new field of research, but it’s also a booming field of research. So what would you say is the element of novelty that your study brings?
Simon: The novelty lies on what we know naturally, because what we’ve known for years and from what pathologists will say about cancer innervation is nerve density in cancer is associated to poor outcome in cancer. So that was known. That is a fact but what we brought was the novelty of our work relates to the mechanisms that are quite surprising in their nature because we were all looking to signaling pathways that could be activated at the nerve cancer phase. And what we found was very, very different. So I think that is the novelty, which is brought by the paper.
Gustavo: I agree totally. It’s novelty and impact. So for the past 50 years, we have been focusing on genes. Cancer is defined as a genetic disease. Changes in genes produce cancer, right, and make cancer more aggressive. And I think that’s true, but it’s not the whole story.
And what we see here is the closing of the loop in this history of cancer nerves. Cancer doesn’t turn on genes or turn off genes. The modulation of the energetic metabolism, and the impact of which is it makes cells metastatic, it’s humongous, is through organelle transfer, horizontal mitochondrial transfer.
And it gives you a whole different view of what cancer is and what we’re going to need to do to be able to modify cancer’s behaviour. Maybe targeted therapies will have their role, but also molecules that modulate nerve function. It’s really important to understand that the modulation of nerves will be necessary to let other therapies become more important.
So again, if you think about impact, you stop chemotherapy, you stop radiation therapy when you start affecting nerves because you can’t take that back. But you are leaving the most important element that cancer uses to kill. So all these therapies are gonna become much more efficient if we learn how to modulate nerve function and understand that that modulation needs to happen through non-transcriptomic ways.
Simon: As you say, Gustavo, that’s bringing a new layer of understanding of what cancer is because we knew for instance that non-cancerous and cancer cells can communicate with each other, can activate signaling pathways, we knew that. And then we found they can even transfer some molecules. For instance, we can transfer some metabolites. We knew that it’s kind of fueling the cancer by giving some metabolites. You give a battery to the cancer cells. But here on this particular setup, it’s like we transfer the power plant. We transfer the way of generating energy from neurons to cancer cells, which is much beyond what we thought. And taking in consideration that neurons are extremely good energy producing organelles. Instead of just sending the fuel, we send the factory and the plan of the factory as well in terms of metabolism.
Gustavo: And it’s not just the how it happens, it’s the impact it has. This horizontal transfer really defines cancer aggressiveness. This is what makes cells have metastatic potential. Through all the mechanisms that we described in the paper.
Alexandra: I’ll admit that this is new territory for me. Although I find it fascinating, I can’t say that I understand the nitty gritty details of nerve cancer cell interplay. So I was wondering if you could please explain the mechanisms associated with cancer nerve metabolic dependencies in cancer progression.
And I know this is like a huge question. But from what I understand from your paper, cancer sort of boosts the neuronal mitochondria and then in turn, neurons transfer those mitochondria to cancer cells.
Simon: That’s right. So that’s a bidirectional discussion. There is really like this connection between cancers and neurons, which is occurring. The power of the data we generated also rely on multiple data sets that Gustavo has generated in his lab, I have generated in my lab, in rat, in mouse, in humans. We always came to the discussion in every data set that if you block the nerve, you block the metabolism.
So that’s the power of the defining and the nerves, on this crosstalk. So that’s one aspect. And another aspect is, during this process, we were able to capture like the big pictures of what the nerve does to the cancer by denervation, especially by Botox denervation, that does block every nerve.
So that’s a way we need to study the impact of the nervous system, into the cancer biology. And it was always pointing, whatever the model, always pointing to the metabolism, and always pointing to the mitochondrial metabolism, mostly bringing to the down direction. Very striking, every data set.
And what was needed to confirm the direct relation between the nerves and the cancer cells was also to do like more simplistic models of nerve cancer crosstalk, that we can study in more detail and to see if it’s a direct mechanism, or if the neurons are just a bystander of something else, given the complexity of the tumour microenvironment.
And that’s where we developed a model of neuronal stem cells to cancer interaction where we mix neuro stem cells and cancer cells. And that allowed us to scale up the co cultures to study in more details, the crosstalk. So that’s what we call the SVZ models in the paper. And it did allow us to get this unprecedented view and generate high quality and high level nerve cancer co cultures to solve this problem.
Alexandra: And did you get the chance to look at what regulates the directionality of this transfer? Like do neurons actively donate mitochondria or are cancer cells effectively extracting them via induced mechanisms, such as tunneling nanotubes, or synapse like structures.
Gustavo: It’s both.
Alexandra: Okay.
Gustavo: I have a picture where you can actually see a neuron, right, donating mitochondria to a cancer cell. And at the same time, on the other side of the image, you see cancer cells throwing tunneling, nanotubes, and stealing mitochondria from the cancer cells. So it’s bi-directional. And again, if we go back in time, it’s really funny but this is exactly what the first paper said. I love this picture because it takes me back to that first paper that just said, cancer cells and nerves like to play with each other. And so what we know today is how they play.
We’ve known for a long time that they were good for each other, that there was a symbiotic relationship. And by the way, Simon did some experiments where we defined that the supernatant and secreted factors were not as important. So we started concentrating on, direct transfer. And I also have another picture, that’s not in the paper, where you see membrane to membrane transfer of mitochondria. You see membrane dissolution and the mitochondria going. So we think that it’s more important for mitochondria, which are relatively big, although you can have huge, and I have anecdotal data from other investigators that mitochondria can be transferred through large exosomes and different types of molecules, right?
So, I don’t believe that there’s anything in nature that is exclusive. I think that there are preferential mechanisms. And I think that the preferential mechanism of transfer requires direct contact.
Simon: Yes. Especially when we talk about neurons because, as you say, we tested like distant versus direct contact and in term of nerve cancer crosstalk, it is contact mediated mostly. Even if really we see some non-contact mediated that’s significant, it’s not like the majority. That’s like flying fish.
Gustavo: You need to understand, the nervous system is the perfect system to do direct contact, transfer. The nervous system, and, we really don’t think about it this way, it touches every single cell of the body. So, we think that nerves go and end, and there’s a space and no. Nerves touch, or are in sufficient vicinity of, all the cells in the body.
The other thing is a lot of effort has been put into, what do neurotransmitters do for cancer? Because we’re thinking of nerves as nerves. We have defined nerves by the fact that they have synapses and transmit neurotransmitters, right, through synaptic junctions. That’s our definition of nerves. But we tend to forget that nerves are also endocrine Neuropeptides can’t go through synapses. They have to be secreted into the microenvironment. And so, what we’re finding now is a new function for the nervous system. And I’m gonna go out on a limb here, but we think, and we’re gonna try to prove, that this is physiology, that this is not a cancer exclusive process. We think this is how the nervous system regulates the energetics of the normal body. But we have a ways to go.
Alexandra: Which would be in line with cancer cells being able to hijack mechanisms, which has been seen in other areas of cancer research before.
Simon: Yeah, that’s a unique opportunity where we discover the physiology through the lens of the disease. Which means we have the tip of the iceberg and there is all the other parts to discover. And that’s what is exciting about this project. As you say, cancer cells will never reinvent anything, they just hijack.
For a long time I’ve been studying epithelial-mesenchimal transition, which is now real development, wound healing development, hijacked by cancer during metastasis. We discovered that before the function in metastasis, but here we are doing the reverse direction and that is super exciting.
Alexandra: Your study has a double value, the development of methodology and also investigates the effects of mitochondrial transfer on cancer cell biology. And you developed the MitoTRACER to permanently label the recipient cancer cells after mitochondrial transfer from neurons. And you’ve mentioned during this conversation that this mitochondrial transfer has a huge impact on the aggressiveness of cancer. So I was wondering, how do neuron derived mitochondria confer increased metastatic abilities?
Simon: Okay, so that’s like two questions in one. Let’s break down what we developed and what the MitoTRACER is, and how we use that to understand the impact of the transfer of mitochondria and how did we leverage this technology to better understand the mechanism.
So what you need to understand about the MitoTRACER is when we went to this metabolic crosstalk between cancers cancers and neurons, that was super interesting. We were able to document the transfer of mitochondria. There is several way to do that. You can simply label genetically mitochondria with a fluorophore, like a GFP, and then you can see this mitochondria going from one cell to another cell, by microscopy imaging for instance. But there are some limits on this methodology.
The first limit is your signal is not conditional to the transfer, so it’s very difficult to curate the data and actually, most of the screened signals will be from your donor cells and you need to identify some of these green signals going into non-green cells as an evidence of the transfer of mitochondria. So that’s difficult to analyse and it’s taking time.
And the other aspect, which was a major bottleneck for this study, because we made the hypothesis that the transfer of mitochondria is driving cancer aggressiveness and will be one explanation of why highly innervated cancers are more aggressive, is that when this mitochondria transfer it to the recipient cells, the signal of this mitochondria disappears over time, is diluted, because the transferring mitochondria is not labeled anymore. Because the label that you used to label this mitochondria is on the nucleus of the donor cells.
So on the nucleus you produce the reporters that go to the mitochondria. It labels them. These mitochondria transfer it to recipient cells and ultimately they are integrated into the recipient cells, but the signal is going to fade away.
And that was a major block to test our hypothesis about the rules of this transfer, in changing the phenotype of recipient cells. Because we were not able to clearly distinguish recipient versus non recipient cells in our system, and isolate the contribution of neurons versus the contribution of neuron’s transfer of mitochondria as well.
So, that’s how we address this problem by developing this technology that permanently marks the recipient cells, and that’s what we call MitoTRACER. We are going to develop that in detail, but basically it consists of a pair of scissors and a light switch. So, what do you have? You have your donor cells. They are labeled it on the mitochondria with a pair of scissors that can make some genetic editing that’s a pre recombinase. And when this mitochondria transfer it to recipient cells, they activate a light switch and they do some genetic editing in the recipient cells. This is activating fluorescence and, as a result, your cells are permanently marked, and it’s kind of stamping A GPS into your recipient cells. It’s like you mark these cells with a GPS and then, based on this fluorescence, you can follow their fate. And that’s what we use to understand the roles of this transfer in cancer aggressiveness in general.
So ultimately demonstrating the role in metastasis through lineage tracing, because we were able really to follow the fate of the cells and their progeny over time. So that was, technology wise, how we enabled that.
Alexandra: I was wondering also if we are to look a bit beyond the increased metastatic potential in the mitochondria recipient cells, that you’ve demonstrated so nicely in the paper, and then the subsequent impact on cell invasion. I was also wondering if you noticed any impact on cell signaling and/or the tumour microenvironment. For instance, do transferred mitochondria alter signaling pathways, or immune evasion in recipient cancer cells.
Gustavo: There’s another paper that is showing that cancer cells actually steal mitochondria from T cells and donate their defective mitochondria (https://doi.org/10.1038/s41586-024-08439-0). Essentially, the T cells are there, they live, but they are functionless. And that’s a big component of the immune inhibition.
So, what we’re seeing is a repeat of non signaling mechanisms that regulate cancer.
Simon: Yes. And to clarify in our specific biological context, using this tool we were able to get some surprising way, we discovered, like the impact was not what we were expecting actually. And you mentioned signaling pathways, that’s not exactly what we found.
The first striking observation is, in the lab, as soon as we got these recipients versus non recipients separated into different co-cultures, we made many clones and we found that the recipient cells were growing on a very different pattern. That was the very first observation. My tech was concerned about the recipient cells not being healthy because they were not attaching to the bottom of the plate. They tend to grow by themselves and detach. And looking more carefully, it’s actually these breast cancer cells, they were forming what we call mammospheres, which is a sign of stemness properties. That’s what stem cells do. They grow in a surface independent manner, and that’s what we found very early. We found these recipient cells behave differently because they like to grow in 3D instead of growing in 2D, like just by themselves. That was the first observation.
I think this dataset about recipient cells being more forming metastasis. When we looked at the more detailed mechanism, the first obvious experiment was to test the invasive capacities of the cells. So we took the recipient versus non recipient on an in vitro setup, on the invasion assay setup, and we did not see a striking difference in the invasive capacities per se. And it was like a little bit confusing at that time, because these cancer cells, when they receive mitochondria, therefore more metastasis. But at the same time, they are not more invasive or there is not big increase of their invasive capacities.
So that’s when we decided to take these cells back to the animal. If they’re not more invasive in vitro on the simple setup, are they more metastatic when we separate them and re-inject them into the animals? And we found yes, yes they do form metastasis. They are not more invasive, but they form more metastasis. That’s actually exciting data at this point.
Gustavo: Yeah, I think that was the breakthrough. But also, it’s not that we didn’t look for signaling mechanisms, and actually I personally looked for 15 years before we found this. So when you look at transcriptomic data, you see the result but you don’t see the how, and this data is available so anyone can go and mine it. Maybe I just missed it.
So you see that 25-year-old data. You see what happens, but you don’t see how it happens or what led to it. And I think for me, the importance of this is, well, finally when we started looking somewhere else, we found that it was non signaling mechanisms.
Simon: Just to clarify that, metastasis is not only about invasion and people always think metastasis as a matter of invasion, but actually the metastatic cascade is much more than that. It’s a very complex journey for the cancer cells.
And cancer cells not only even needs to be invasive to leave the primary tumour, but most importantly, they need to survive throughout the process of metastasis and ultimately outgrow on secondary sites that could be very different from the primary site.
For instance, a primary tumour will be on a very different environment than a metastasis growing on the brain where, for instance, the metabolic environment and the glucose resources are much more limited.
And another aspect is when these cancer cells leave, they have to go through the bloodstream, like as a highway to disseminate to the organism. It’s a very unnatural environment for a carcinoma cell, which is of epithelial origin, which usually are always growing on a substrate to evolve in a liquid environment.
And there are two major bottlenecks in the blood, to metastasis. It’s the oxidative stress and the sheer stress. And when you look at the data, 99.9%, even more, of cells that reach the blood will ultimately not form metastasis. And the reason behind that is they die during the process. They cannot survive this stress.
And what we found is the transfer of mitochondria provides the recipient cells with this metabolic plasticity that we know is associated to resistance, to oxidative stress, resistance to sheer stress, that are two main factors of metastatic attrition during metastatic progression.
And I really want to bring that to your answers because it really changed the way we think about metastasis. Maybe we should not target the ultra invasive cells that are running very fast, because at the end 99.9% of them will fail. There is this subset of cells that are not only invasive but also plastic, in terms of their metabolism, which not only runs fast, even if it’s not like the ultimate requirement, but survive during the journey of metastasis. That is cells that we need to therapeutically target. And right now most of the approach is really to target invasion, invasion, invasion. And we know it does not work very well.
Gustavo: And this is Darwinism at its best. This is natural selection. The cells that survive are the cells that have the ability to survive, and that’s what the mitochondria does. And we still have ways to go to understand how it does.
I mean the metabolic plasticity is obvious, right? But how it affects the capacity to survive sheer stress and oxidative stress, we still don’t know. That’s the future, obviously. We’ve been doing basic science for so many years. I think it’s time to concentrate a little bit in the clinic right now.
I think that knowing what the mitochondria does to influence oxidative stress, it’s good, we will do it. But I think that we know already enough to understand that nerves do provide cancer cells with, if you want to call it, superpowers. Cells become super athletes through this.
And I think that that neural modulation needs to be a part of therapy as soon as possible. And we are lucky that there are so many neurotoxins in nature, and in warfare, that can be tested to see how to modulate, and again with a clinical emphasis.
The other way to see this is, the nerves are a road. They’re superhighways through the body, that epithelial cells, and all other cells, gladly accept. They accept the guidance of the nerves through mitochondria and many other mechanisms.
So we have to start thinking about or tropic nano molecules where we can put whatever we wanna put inside, targeted therapies, chemotherapy, whatever, because this will get to every single cancer cell, in ways that we cannot do today. It’s actually not the blood vessels that do this delivery, it’s actually the nerves.
So, I want to emphasise that, it’s good to know the ultimate mechanism, but sometimes we get stuck there and I think we have a clinically targetable element right now, and we have to start designing. We’re looking for collaborators, so if anybody’s interested, email, call.
Alexandra: You do show in your paper that the innervation reduces invasive tumour progression, in your models. So how feasible do you think it is to therapeutically disrupt nerve tumour mitochondrial transfer without damaging normal neurons’ function?
Simon: That’s like targeting the nerves. I mean, beyond the philosophical question, there is this clinical therapeutic application because do we target neurons? Do we target the recipient cells? Obviously targeting the neurons come with some level of toxicity that needs to be managed. But as Gustavo said, there are so many highly specific nature designed neurotoxins that could be used. And what we used in the paper was Botox as a general denervation mechanism that worked very well. Other people have shown similar outcomes, especially Gustavo with your clinical trial (https://doi.org/10.1002/pros.23454).
Gustavo: One of the things I did 15 years ago, I didn’t propose Botox as a means of treating cancer, but today I’ll be more aggressive. So what I did 15 years ago, I just did it because I wanted to know if the biology that I found in vitro and in rats and in mice existed in humans, and I did prove that you put Botox into a prostate cancer and it starts killing cells, they undergo apoptosis (https://doi.org/10.1002/pros.23454).
Let’s take radiation therapy. So, radiation therapy actually induces axonogenesis because it creates damage in the body. So radiation therapy, while it’s killing cancer cells through DNA damage at the same time, it’s increasing what could defend the cancer cells. So let’s design a clinical trial, neoadjuvant Botox to radiation therapy. Which would make radiation therapy more efficient and we could even lower doses. That’s a clinical trial in the waiting. Surface lesions in the cervix, in the bladder, in the skin, in the head and neck. Can you induce regression through denervation with Botox? I’m pretty sure it will. These are things that can happen tomorrow.
Simon: And to speak about the generality, how broad is this concept for the audience? I mean, to clarify, I’m not aware of any cancer which is not innervated. Innervation in cancer is a general process. We are not talking about only a few subtypes of cancers that could have nerves into their stroma. This is a general mechanism, which applies to every cancer, from my knowledge at least.
Alexandra: Gustavo, you mentioned earlier that there’s a need to move the discoveries into the clinic. And that very well aligns with one of the things that was seen as an outcome from our cancer neuroscience conference last year. But another thing that was discussed as part of a panel discussion at that conference was that there’s a need to look at the way that clinical trials are structured and there was like a consensus that there might be a need to have a slightly different setting for the clinical trials for them to best fit for this research field. What’s your opinion on this?
Gustavo: I totally agree. We have so many tools we didn’t have three years ago. Let’s start using them. There has to be a faster way of doing things. Listen, we could use intermediate endpoints, if necessary, to look at things. Or at least as guidance. It’s dangerous sometimes to use intermediate endpoints. I’m a pathologist, I live with intermediate endpoints, but I fully agree. We can’t start today and have the first results, of basic things, in seven years.
And again, because of what we have found, we could focus the clinical endpoints to very aggressive disease. Now, let’s define aggressive disease. Most biomarkers look at the cancer cells, and what they’re measuring is the genetic load that this cancer has gone through. But if we also accept, you know, I do biomarker discovery and I concentrate on non-cancer biomarkers. I measure the host. One of the things I measure is nerves.
So, if we design these studies, we first define what aggressive cancer is and how we’re going to select these patients. And then concentrate on the very aggressive cancers, we’ll have results much quicker. Because, you know, prostate cancer is the leading cause of death for males. But do you know what the mortality for prostate cancer at five years is? 1%. Because we’re calling a bunch of things that are not cancer and that have very little aggressive potential, cancers. So, I think that we need to focus on this population of very aggressive cancers and start testing neural modulation as soon as possible.
Alexandra: Thanks both of you for sharing some insights from your study with me. I’m glad that I had this opportunity to discuss such an interesting paper with the minds behind designing the study. Looking back, which would you say was the key experiment?
Simon: In my view, that’s a mix of three elements. I think the Botox, the innervation, in different type of setup. Again, rats, mouse, humans, gave the big pictures of the story. The MitoTRACER brought the mechanistic answer, and the collaboration between Gustavo and me, has been an incredible key on the success of this study.
Gustavo: I’ll say the key to this paper was the fact that Simon published another paper (https://Doi.org/10.26508/lsa.202101261), and I sent him an email congratulating him, and he said, you need to come and give a talk. And we started talking and he showed me the data that he had in breast cancer and I told him some of the 15-year-old data I never published. I did all the denervation experiments. I have all the transcriptomic data, and the key was that. We connected and in two years we did all the data for this paper.
Alexandra: That’s impressive. Well, Simon, Gustavo, thank you so much for taking the time to share your research results with me, and with our listeners, and for giving us the opportunity to learn a bit more about the blooming field of cancer neuroscience.
Gustavo: Thank you for having us.
Simon: Thank you very much for the invite.
Alexandra: We really hope that you enjoyed listening to this fantastic research story and that you learned something new from us today. If you have any follow-up questions regarding this conversation, please don’t hesitate to contact Simon or Gustavo by email.
If you enjoyed this episode, you may be interested in the EACR Conference on Cancer Metabolism to take place in Bilbao, Spain, between 06-08 October 2026. You can find out more about the programme on the conference website at www.eacr.org/conference/cancermetabolism2026. Please note that the abstract submission deadline is 29 June 2026.
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