Chronic inflammation is a well-established driver of cancer development, and emerging research suggests that it plays a significant role in neuroendocrine tumourigenesis—the process by which neuroendocrine tumours (NETs) form and progress. While genetic mutations are a known contributor to NETs, inflammation can create an environment where tumours are more likely to arise, grow, and evade the immune system.
Chronic inflammatory conditions such as inflammatory bowel disease (IBD), chronic pancreatitis, and chronic infections like Helicobacter pylori (H. pylori) and hepatitis viruses have been linked to an increased risk of developing NETs. Persistent inflammation can lead to DNA damage, immune suppression, and the activation of cancer-promoting pathways, ultimately supporting tumour formation.
This article explores how chronic inflammation contributes to NET development, the role of infections and autoimmune diseases, and how targeting inflammation could help prevent or slow the progression of NETs.
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.
Inflammation is an essential biological process that helps the body fight infections, heal injuries, and eliminate harmful agents. It is a protective mechanism that involves the activation of immune cells, the release of chemical signals, and increased blood flow to affected tissues.
While acute inflammation is short-lived and resolves once healing occurs, chronic inflammation is a long-term immune response that can persist for months or years. This prolonged inflammation can lead to tissue damage, genetic mutations, and alterations in cell function, making it a significant factor in cancer development.
It’s important to understand the difference between acute and chronic inflammation and its role in how the body heals.
Chronic inflammation does not simply cause cancer, but it increases the risk of tumour development by damaging DNA, supporting tumour-promoting pathways, and suppressing normal immune surveillance mechanisms that would otherwise detect and eliminate abnormal cells.
Chronic inflammation plays a role in tumour development through several mechanisms:
Several key molecular pathways are activated in response to chronic inflammation, contributing to cancer development:
When these pathways remain persistently active, they create conditions that encourage tumour development and progression.
Cytokines are chemical messengers released during inflammation, playing a crucial role in how NETs develop. Inflammatory cytokines such as IL-6, IL-1β, and TNF-α drive tumour growth by:
Chronic inflammation leads to persistent oxidative stress, increasing the risk of genetic mutations in neuroendocrine cells. Over time, these mutations disrupt tumour suppression mechanisms, allowing NETs to form and spread.
Inflammation reshapes the tumour microenvironment by:
There are several inflammatory conditions associated with NETs. Keep in mind that research into NETs is always improving our understanding of the condition. New inflammatory conditions may be discovered in the future.
Patients with Crohn’s disease and ulcerative colitis are at a higher risk of developing small intestine and colon NETs due to chronic gut inflammation.
Long-term pancreatic inflammation in chronic pancreatitis creates a tumour-prone environment, leading to an increased likelihood of pNET formation.
Chronic hepatitis B and C infections cause liver inflammation and fibrosis, which may contribute to NET formation.
Fortunately, inflammation can be treated. Preventing and treating the root causes of conditions can yield better outcomes for patients.
Researchers are exploring the role of NSAIDs, corticosteroids, and TNF-α inhibitors in reducing NET growth and lowering cancer risk in patients with chronic inflammation.
A diet rich in omega-3s, antioxidants, and plant-based foods may help lower inflammation levels, alongside regular exercise and smoking cessation.
There are also several emerging therapies that might be able to target and treat inflammatory pathways. These treatments are still in early stages, and more will be known about them in the future,
Ongoing studies aim to determine whether controlling inflammation could slow NET progression or prevent tumour formation in high-risk patients.
Inflammatory biomarkers, such as C-reactive protein (CRP) and IL-6, may help prompt detection of NETs earlier in patients with chronic inflammatory conditions.
Combining immunotherapy with anti-inflammatory agents is being explored as a potential strategy for improving NET treatment outcomes.
Chronic inflammation plays a significant role in NET development and progression. Understanding its effects on DNA damage, immune suppression, and tumour growth may lead to improved prevention and treatment options for NET patients. As research advances, targeting inflammation could become a key strategy in reducing the burden of NETs and improving patient outcomes.
Further information and support for people diagnosed with NETs is available by calling the NECA NET nurse line.
