Neuroendocrine tumours (NETs) are a rare and complex type of cancer that can develop in various parts of the body. Unlike other cancers, NETs arise from neuroendocrine cells, which play a dual role in the nervous and endocrine systems by producing hormones that regulate bodily functions.
The development of NETs involves a combination of genetic, molecular, and environmental factors, leading to a wide range of tumour behaviours, from slow-growing to highly aggressive forms. This article explores how NETs form, their unique characteristics, and the latest research in understanding and detecting these tumours.
Neuroendocrine Cancer Australia (NECA), is dedicated to assisting individuals diagnosed with NETs and their loved ones. NECA offers a wealth of resources, educational programs, and advocacy efforts aimed at deepening the understanding of NETs, improving patient care, and encouraging research advancements. Patients can engage with NECA’s comprehensive support and information by calling the NET nurse line.
Neuroendocrine tumours originate from neuroendocrine cells, which are found throughout the body, particularly in the gastrointestinal (GI) tract, pancreas, and lungs.
These tumours can behave very differently from more common cancers—some remain slow-growing and may not spread for years, while others can be aggressive and metastasise rapidly.
One of the defining characteristics of NETs is that they can be either:
Unlike carcinomas or sarcomas, which develop from epithelial or connective tissues, NETs originate in hormone-producing cells, leading to a unique clinical presentation.
While many cancers rely on genetic mutations that drive unchecked growth, NETs often develop through disruptions in hormonal pathways and signalling networks, which makes their behaviour unpredictable.
Neuroendocrine cells are specialised cells that share characteristics of both nerve and hormone-secreting cells.
They regulate essential processes like digestion, metabolism, and blood pressure by releasing hormones into the bloodstream.
When these cells undergo genetic mutations or environmental changes, they can start to grow uncontrollably, forming tumours.
The development of NETs is often driven by genetic mutations that affect cell division, hormone regulation, and tumour suppression mechanisms. Some of the key genetic alterations linked to NETs include:
While most NETs occur sporadically, some cases are linked to hereditary conditions, including:
Genetic testing can help identify individuals at higher risk, allowing for early detection and monitoring.
While the underlying causes of NETs are unknown, there are a range of risk factors that can contribute to the disease, ranging from genetic predisposition to lifestyle factors.
While some NETs are inherited, the majority occur sporadically with no clear genetic link. Sporadic NETs may arise due to a combination of random mutations, environmental exposures, and lifestyle factors.
Although the exact environmental triggers for NETs are still under investigation, potential risk factors include:
Hormonal imbalances and metabolic disorders may contribute to NET development. Research suggests that conditions like chronic hypergastrinemia (excess stomach acid production) and insulin resistance may create an environment that supports tumour growth.
NETs are typically classified into low-grade (G1), intermediate-grade (G2), and high-grade (G3) tumours, based on how quickly they divide.
The Ki-67 proliferation index, a measure of how many tumour cells are actively dividing, helps determine tumour grade and predict behaviour. High Ki-67 levels indicate faster-growing tumours that require more aggressive treatment.
NETs can metastasise to distant organs, most commonly the liver, bones, and lymph nodes. Tumours that invade local tissues may remain confined for years, while aggressive NETs spread rapidly through the bloodstream or lymphatic system.
When assessing the hormonal activity of NETs, it’s important to understand how their functional versus non-functional classification can change.
Functional NETs can cause a range of symptoms depending on the hormones they produce:
There are a range of key signalling pathways that can be used to treat NETS. NETs rely on several molecular pathways for growth, including:
New biomarkers, such as NETest (a gene-expression blood test, not yet available in Australia) and circulating tumour DNA (ctDNA), are being developed to improve early detection and treatment response monitoring.
Neuroendocrine tumour development is a complex process influenced by genetic, environmental, and molecular factors. While NETs remain challenging to diagnose and treat, ongoing research continues to improve our understanding, leading to better detection methods and more effective therapies.
With increasing awareness and advances in medical science, the future of NET management in Australia and worldwide looks promising.
Local Australian research institutions and global collaborators are conducting studies to:
Advancements in genomic screening and biomarker research may allow for earlier detection of NETs before they cause symptoms. Preventive strategies, including lifestyle modifications and targeted screening for high-risk individuals, are also being explored.
Further information and support for people diagnosed with NETs is available by calling the NECA NET nurse line.
