2024-03-03 15:34:15
An estimated 7,000 people in Germany develop brain tumors every year (1). Older people and, particularly often, children are particularly affected. Not all cancer is malignant, and the mostly benign meningiomas of the meninges rarely pose a health risk. However, if a brain tumor is malignant, then even more so – the prognosis here is usually particularly bleak.
What doesn’t make things any better: In contrast to other types of cancer, there are no clear causes for brain tumors and therefore no preventative measures. But recently, science may have begun to catch up in the fight once morest brain cancer, which might be groundbreaking for cancer therapies in general. Hero of the story: neuroscience.
Nerve cells control tumor cells – and vice versa
In the renowned specialist journal Cell A large review article was recently published in which the relationship between the nervous system and tumors was discussed (2). The wealth of data from which the authors drew paint a picture that would surprise even most experts: the development of tumors apparently requires help from the nervous system. You have to know that a tumor is not a dead mass that grows. Rather, a tumor is an active system that creates an individualized microenvironment in which it can flourish.
This environment includes, for example, synapses with normal nerve cells in the brain, as well as ion channels. Neurons act on the cancer cells through the ion channels. The goal of this structural and electrical connection with the brain: an adaptive responsiveness of the tumor that closely resembles healthy neuroplasticity and thus optimal growth conditions. Studies have shown that when the synaptic connection between the tumor and the brain becomes stronger, the probability of survival of patients decreases (3).
A brain within a brain
It has long been standard knowledge that tumors use messenger substances that lead to the growth of new tumor blood vessels (angioneogenesis). The cancer creates its own express supply of nutrients. But the fact that it also uses messenger substances from nerve cells is a completely new situation. The adaptive, synaptic system that tumor cells can form with brain cells can in turn also arise in the tumor itself. The process resembles the formation of a ‘brain within a brain’. Such synaptically self-crosslinking tumors have been found to be more resistant to chemotherapy, which further reduces the chances of survival once morest such types of tumors.
Preclinical study results from ‘Cancer Neuroscience’
Nerve cells also play a role in the development of cancer outside the brain. Perineurale Invasion refers to the phenomenon that tumor cells migrate into peripheral nerves, where they can grow particularly well for reasons that are still unknown. The authors of the Cell Articles suspect that the proximity to the messenger substances that nerve cells release is a survival criterion for the tumor cells. Prostate, breast and pancreatic cancers in particular are susceptible to perineural invasion and show greater aggressiveness when it occurs. In studies where the nerves responsible for sensory sensations were removed from around the pancreas, the growth of pancreatic cancer even slowed (4). It has also been shown that the release of nerve growth factor (NGF) by the tumor itself causes peripheral nerves to grow towards the tumor (5). A connection between NGF and nerve ingrowth into the tumor environment has also been found in cases of stomach cancer.
Perineural invasion, on the other hand, is promoted, for example, by the glial cell line-derived neurotrophic factor (GDNF) (6). In the case of prostate cancer, it has been known since 2019 that the tumor attracts neuronal precursor cells from the brain to the periphery (here to the prostate), where these dynamic cells grow. All of these principles are similar to angiogenesis: the cancer gets what it needs by sending, manipulating and sensing molecular signals. These are usually normal, physiological processes that the tumor cells use in abnormal ways (see illustration). One might also speak of the tumor controlling other cells.
In normal conditions (left), neuronal activity promotes the incorporation of myelin (an insulating fatty layer) by glial cells (blue), was improves information processing. In the case of a glioma, i.e. a brain tumor (right), degenerated glial cells use neuronal activity to create a tumor network instead of a neuronal network. (from Winkler et al. 2023)
New research centers for a new discipline
Die Neurooncology is a comparatively young discipline for which there is not even a dedicated specialist. And yet science is already one step further. This is currently emerging from neuro-oncology Neuronkoimmunologie, which is intended to research the issues described here. In Heidelberg this is exactly what is being founded for this purpose European Center for Neuro-Oncology. The name shows how rapid the development is. After years of planning, the name is purely neuro-oncology, but those involved in the center are already talking regarding the content Cancer Neuroscience.
Where we stand
Cancer research has so far been characterized by only achieving slow and small successes. Scientifically, cancer is still an incredibly tough nut to crack. Since all of the results described here only come from preclinical studies, it is still too early for high hopes. However, the pace is currently picking up more speed than ever and the formation of large research centers always speaks of a spirit of optimism. If the preclinical evidence is confirmed, this might happen Cancer Neuroscience will therefore soon prove to be a new direction on the research map.
Sources:
(1) Primary tumors of the brain and spinal cord. German Cancer Society.
(2) Winkler, F., Venkatesh, H. S., Amit, M., Batchelor, T., Demir, I. E., Deneen, B., … & Monje, M. (2023). Cancer neuroscience: State of the field, emerging directions. Cell, 186(8), 1689-1707.
(3) Krishna, S., Choudhury, A., Seo, K., Ni, L., Kakaizada, S., Lee, A., … & Hervey-Jumper, S. L. (2023). Glioblastoma remodeling of neural circuits in the human brain decreases survival. Nature617, 599–607.
(4) Saloman, J. L., Albers, K. M., Li, D., Hartman, D. J., Crawford, H. C., Muha, E. A., … & Davis, B. M. (2016). Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer. Proceedings of the National Academy of Sciences, 113(11), 3078-3083.
(5) Anand, U., Otto, W. R., Casula, M. A., Day, N. C., Davis, J. B., Bountra, C., … & Anand, P. (2006). The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons. Neuroscience letters, 399(1-2), 51-56.
(6) He, S., Chen, C. H., Chernichenko, N., He, S., Bakst, R. L., Barajas, F., … & Wong, R. J. (2014). GFRα1 released by nerves enhances cancer cell perineural invasion through GDNF-RET signaling. Proceedings of the National Academy of Sciences, 111(19), E2008-E2017.
(7) New center for neuro-oncology in Heidelberg. German medical journal from 11/28/23
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