Can cancer's development alter our brains?

People diagnosed with cancer also frequently develop mood disorders like depression, but sometimes before they even know they have the disease, ruling out just having cancer as a cause. But could the reason be that their cancer is in conversation with, and manipulating their nervous system? Paola Vermeer is a researcher at the University of South Dakota. She’s found that developing cancers seem to form associations with nearby nerves, and strike up a relationship. The nerves can grow into the tumour, which can “listen to” and respond to the signals issuing from those nerves; but even more intriguing is that the cancer seems to be sending messages back to the brain via those nerves, altering brain activity and chemistry, and therefore potentially also mood. She’s just published a paper in the journal eLife documenting how this seems to happen. It might, she argues, lead us to new ways to approach the management of cancer…

Paola - So we've known that tumours actually can infiltrate the nerves and that's associated with a poor prognosis for many cancers. But what we're now learning is that it happens the other way around, that the nerves can actually infiltrate the tumours as well. They are two very separate processes. So when the tumour contacts the nervous system, it can utilise that as almost a roadmap to get to different parts of the body and metastasize. So, it's a route for metastasis, but when the nerves infiltrate the tumours, they can actually release factors that further promote increased proliferation of the tumour and allow it to grow.

Chris - So it's almost like in the same way as the nerve would talk to a target organ in the body, like a muscle, it can talk to the tumour and provoke behavioural change on the part of the tumour?

Paola - Oh, absolutely. We've started to define some of these molecules that are used in these conversations. So there's actually talk from the nerves to the tumours and then from the tumours back to the nerves. It's a very active communication where the two entities impact each other.

Chris - And what about higher centres? What about, if you have a sensory nerve contacting a tumour and obviously the job of a sensory nerve would normally be to relay information centrally up to the brain. Does that actually get reflected in a change in behaviour then?

Paola - Yes, absolutely. And we were very intrigued by this because cancer patients really suffer a decline in their mental health. And we can study this by looking at behaviour in mice where we implant tumours. So we saw that the brain was changed and the mouse behaviour was also changed.

Chris - When you say the brain was changed, what did you actually see?

Paola - We saw that the brain regions that were connected to the nerves in the tumour, had a very high activity. They were firing a lot more than the same regions of the brain from a non-tumour bearing animal.

Chris - How was that reflected in behavioural change?

Paola - The behavioural tests that we use were really reflecting the wellbeing of the animal. And so their behaviours for those animals that had tumours went significantly down as the disease progressed. So they wouldn't make a good nest or they wouldn't eat a cookie because they were essentially depressed.

Chris - And this is not just because tumours are painful, because as we know when you have a tumour growing invasively through various tissues, that is extremely uncomfortable. It wasn't just that in these animals, they're in pain, that's why they withdraw socially?

Paola - No. In fact, we tested that, and we had a group of mice that we gave a tumour to, but then we treated them with a medication for their pain and that did not fully restore their normal behaviour. So it's not only pain information that is being relayed to the brain, there's more to it than just that.

Chris - And what about different types of tumour? Because some are more nerve-like in their behaviour and the sorts of tissues of origin and the things they make, the tumours themselves. So would you expect that some tumours are probably going to have these sorts of effects to a greater extent than others?

Paola - Yes. And as you said, the location of the cancer can really dictate not only the extent of how many nerves infiltrated, but also what type of nerves. So, all the tumours that we've looked at so far are innervated, but the types of nerves could be different and therefore the influence of the nerves on the cancer could also be different.

Chris - What do you think this tells us then? Does this sort of show us a way that we should manage cancer differently or does it open up different avenues for management?

Paola - Absolutely, It tells us that so far all the cancer medications that we have completely ignore this nerve component of the tumour. So that isolates the nerves as a therapeutic target. And since we know some of the molecules, we can design drugs to target them. But it also tells us that beyond the local tumour, we need to consider what the connections to the brain are and how we can therapeutically mediate changes in behaviour in cancer patients as well.

Chris - And looking at it the other way around, if you make the person's mood better, does that affect the behaviour of the tumour?

Paola - We haven't tested that directly, but given the bidirectional nature of these communications, I would expect that yes, if you can change the neurons in the brain and the behaviour that should have an impact on the tumour itself.

Chris - Why has no one looked at this before?

Paola - The understanding that nerves are in cancers is relatively new, as surprising as that sounds. So we are just at the early stages of understanding, not only that the nerves are there, how are they getting there? What are they doing? And what other neural components are they connected to? It's a very young field.