Tumors Manipulate Neuronal Signals for Personal Gain

Targeting the interactions between neurons and cancer cells may be a powerful strategy in future cancer treatments.

Neurons promote cancer growth in the brain, pancreas, prostate, skin, and stomach, according to a study published in Trends in Cancer.

“There is no part of the body that isn’t well innervated,” said study co-author Michelle Monje. “The nervous system is an extremely arborized tree that reaches every aspect of every tissue and contributes importantly to tissue development. Those growth signals are already there, so why shouldn’t cancer cells co-opt them?”

Cancer treatments frequently cut off the nutrient supply routes of tumors. Investigators have questioned whether targeting nerves via analogous therapies or by blocking secreted neural growth factors could be viable treatment strategies. However, these approaches pose a challenge because growth-promoting signals vary by neuron and cancer type, according to the investigators. Additionally, it can be dangerous to block neural activity.

“In the brain, modulating neuronal activity isn’t a great option because we don’t want to silence the brain. Brains need to be active and functioning,” Monje said. “But we can interrupt the specific molecular pathways that are being co-opted by the tumor.”

In prior studies, Monje found that both adult and pediatric glioma cells grew at a faster rate when adjacent to highly active neurons.

In a different study published in Cancer Cell, investigator Timothy Wang found that recruitment of nerves into the tumor microenvironment is necessary and sufficient for stomach cancer progression. The findings suggested that blocking a neurotransmitter in the nerves that line the stomach could be a novel therapy.

“Seeds don’t tend to grow in the air, they have to be in the right soil,” Monje said. “Cancers are very much like that. They have to be in the right microenvironment.”

Although the findings show promise, the role of neurons have only been examined in a handful of cancers. More research is needed to understand the full molecular details of cancer-nerve partnerships, according to the study.

“As our mechanistic understanding grows, neural targets in the cancer microenvironment may prove crucial for effective disease control,” the authors concluded.