Chronic inflammation is increasingly recognized not only as a hallmark of many diseases but also as a key contributor to cancer development.

Unlike acute inflammation, which is a beneficial and self-limiting physiological response to injury or infection, chronic inflammation represents a prolonged, dysregulated state that can have deleterious effects on tissues.

Distinguishing Acute and Chronic Inflammation

Inflammation serves as the body's defense system, orchestrating removal of pathogens and injured cells and stimulating tissue repair. Acute inflammation is rapid, intense, and transient, involving granulocytes and mediators that resolve the insult and restore homeostasis.

In contrast, chronic inflammation can arise from unresolved acute inflammation or continuous exposure to irritants, infections, or autoimmune activity. It is characterized by persistent immune cell infiltration, tissue remodeling, and release of pro-inflammatory cytokines that create an environment conducive to cellular changes favoring tumorigenesis.

Molecular and Cellular Mechanisms Linking Chronic Inflammation to Cancer

The tumor microenvironment (TME) shaped by chronic inflammation includes immune cells, stromal cells, signaling molecules, and extracellular matrix components. Key inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukins (IL-1β, IL-6, IL-8), and chemokines perpetuate a cycle of cellular stress and repair.

This environment induces oxidative stress through reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can damage DNA, causing mutations and genomic instability—hallmarks of cancer initiation.

In parallel, chronic inflammation activates signaling pathways including nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and hypoxia-inducible factor 1-alpha (HIF-1α). These transcription factors regulate gene expression that promotes cell proliferation, survival by inhibiting apoptosis, angiogenesis, and metastasis.

For example, NF-κB drives expression of anti-apoptotic proteins and inflammatory enzymes like cyclooxygenase-2 (COX-2), which support tumor growth and progression. Immune suppressive cells recruited into the TME hinder effective anti-tumor immune responses, enabling cancer cells to evade immune surveillance.

Environmental and Infectious Contributors to Inflammation-Driven Cancer

Certain infections and environmental exposures exemplify how chronic inflammation predisposes to cancer. Persistent infections with Helicobacter pylori in the stomach lead to gastritis and gastric cancer; chronic hepatitis B or C infections cause liver inflammation, fibrosis, and hepatocellular carcinoma.

Autoimmune conditions such as inflammatory bowel disease (IBD) increase colorectal cancer risk due to sustained mucosal injury and inflammatory cell infiltration.

Additionally, obesity and associated metabolic dysfunction generate systemic low-grade inflammation that promotes cancers of the colon, pancreas, and liver. This systemic inflammation involves adipocyte-derived cytokines and altered immune cell function, creating a pro-tumorigenic milieu across multiple tissues.

Chronic Inflammation as a Target for Cancer Prevention and Therapy

Given its central role in cancer development, chronic inflammation offers a target for preventive and therapeutic strategies. Anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs) have demonstrated efficacy in reducing incidence of certain cancers, notably colorectal cancer.

Novel interventions seek to modulate inflammatory signaling pathways and cytokines or enhance immune system function within the tumor microenvironment.

Emerging research highlights the benefit of combining chemotherapy with anti-inflammatory treatments to improve therapeutic responses and patient survival. Understanding individual genetic and epigenetic factors that influence inflammatory responses may further tailor prevention and treatment approaches.

Smouldering inflammation in the tumour micro-environment promotes malignant cell survival, angiogenesis and metastasis. — Alberto Mantovani, Cancer-Related Inflammation (2008).

Chronic inflammation represents a critical bridge between sustained immune activation and cancer development. Persistent inflammatory processes induce molecular and cellular changes that facilitate oncogenic transformation, tumor growth, and immune evasion. Recognizing and addressing the mechanisms by which inflammation promotes malignancy holds promise for improved cancer prevention, diagnosis, and therapy.