Hitting a nerve: research suggests cancer can hijack neurons to aid growth

Photo Source: Gerry Shaw, Wikimedia Commons

Cancer, a term encompassing a myriad of diseases characterised by the rapid growth and uncontrollable spread of abnormal cells beyond their usual boundaries, remains one of the most formidable challenges in modern medicine. According to the World Health Organization (WHO), cancer is a leading cause of death worldwide, accounting for approximately 10 million deaths in 2020. 
In a ground-breaking revelation, scientists have unearthed mechanisms by which cancer cells may promote their growth and spread: the hijacking of neurons, also known as perineural invasion (PNI). PNI is the spread and growth of cancer cells in or around nerves. Previously, nerves were believed to be collateral damage of tumour growth, passively transporting cancer and its associated pain. However, in the 1990s, pathologist Gustavo Ayala, discovered that nerves grew little branches (neurites) that extended out towards cancerous cells, actively pursuing a connection whereby, upon contact, the cancer would travel along the nerves.
Recent research elucidates how cancer cells hijack existing neuronal processes to fuel their growth and self-preservation. Various experiments have observed tumour cells turning into neurons, acquiring neuron-like features, or even forcing neurons to change their neuronal identities. Cancer cells have been found to capitalise on neurotransmitters and neuropeptides released by nerves, leveraging these signalling molecules to enhance their own survival and invasion. For example, nerve growth factor (NGF) is a neuropeptide that helps promote the growth, development, and differentiation of nerves. However, NGF released by cancer cells attracts nerve fibres towards tumours, fostering a supportive environment for unchecked proliferation. 
Neurons have various direct and indirect effects on tumours that often support cancer growth. Neurons may suppress immune activity to keep themselves safe, as excessive inflammation is damaging for nerves.  Additionally, nerves provide routes for cancer dissemination whilst offering a safe harbor; tumours can hide themselves in nerves, where they are guarded from immune attacks and medication before re-emerging. Tumours may also co-opt neuronal processes used by, for example, pacemaker neurons in the heart, to generate their own rhythmic waves of electrical activity, which pulse through the tumour to orchestrate cancer growth and survival. 
The clinical implications of this phenomenon are profound. PNI is associated with poor prognosis and treatment resistance in various cancers. By understanding the underlying mechanisms of PNI, researchers may develop targeted therapies to disrupt cancer-neuron interactions and halt tumour growth, improving patient outcomes. Current treatment methods for cancer are effective but have detrimental effects on non-target neurons. Looking ahead, the complexity of cancer-neuron interactions poses formidable obstacles to developing treatments but also opens new avenues for therapeutic interventions by providing new drug targets. For example, drugs with established safety profiles, like beta blockers, are being considered for the treatment of cancer, where they may disrupt signals from sympathetic nerves, which drive cancer progression in various cancers, like breast, pancreas and prostate.
It is important to note that there is still, and will likely never be, no ‘silver bullet’ for cancer treatment. Cancer treatments will likely entail uniquely-tailored drug cocktails to control and inhibit cancer growth. It will be interesting to see how researchers will pave the way for innovative treatments that promise to transform the landscape of cancer therapy upon further investigation of PNI.