Nerves control everything from your heart rate to muscle movement to the fight-or-flight stress response.
“Nerves are critical to body function,” says head and neck surgeon Moran Amit, M.D., Ph.D. “It makes sense that they also play an active role in tumor biology, but until the last decade, nerves were really considered innocent bystanders to cancer.”
Amit is leading groundbreaking research into the role nerves play in cancer development. We spoke to him about his work and the up-and-coming field of tumor neurobiology.
What do we already know about the role nerves play in cancer development?
Not much. The way that nerves impact cancer development, inception and progression has only been studied intensively for the last decade or so. Prior to that, the thinking was that nerves acted as a passive highway, or conduit, for tumors to spread.
But within the last 10 years, there’s been a change. A couple of landmark studies showed that nerves are critical to cancer development. Our group showed that certain branches of the nervous system are critical for oral cancer progression. Others found that nerves play an active role in prostate cancer initiation and regulation of breast cancer.
One of the challenges with nerves – and the reason they may have been overlooked for so long – is that nerves are the longest cells in the body. As cancer biologists, when we study tumor specimens, we just see nerve endings. The actual neurons are far away from the tumor – they’re upstream, so to speak.
Can you explain your recent research findings?
We found that cancer essentially hacks the nervous system and reprograms the nerves to its own advantage. Our study found this nerve-hacking taking place in a subset of head and neck cancers that have a mutation in the p53 gene, which is the most common gene mutation linked to cancer.
Once this happens, neurons in the tumor microenvironment acquire new features that boost tumor growth. The really interesting thing is that we found this nerve involvement was happening before malignant transformation, when the cells were starting to develop the wrong way, but still weren’t cancer yet.
What are your next steps for this research?
Now we’re working to understand the mechanism behind this nerve-hacking and see if it’s happening in other cancer types, too. Ultimately, we want to figure out if nerves can be targeted to inhibit tumor growth or to enhance our current approaches to treatment, as an addition to other therapies.
We’re finishing up some preclinical research to see if we can target nerves alongside immunotherapy. If our findings show this is a safe and effective approach, we’ll move toward clinical trials.
How are nerves targeted to treat other diseases?
Many drugs already exist to target nerves. For example, beta blockers have been widely used for almost a century to treat high blood pressure. They work by targeting specific neural inputs. Botox injections are another example. They artificially induce paralysis by deactivating the nerve.
The exciting thing is that we don’t have to start from scratch. We’re looking to repurpose existing drugs and approaches that target the nervous system and use them for cancer.
What else is important for patients and caregivers to know?
Targeting nerves is relatively affordable, safe and sound. I don’t think that we’re going to cure cancer by targeting nerves, but it could help slow tumor growth and reduce recurrences. I think it could also impact patients’ quality of life.
In many cases, cancer is painful and debilitating. Nerves play an important functional role in pain. If we can block or slow down the process of neural involvement in cancer development, we may be able to give patients living with cancer a better quality of life as well.