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Inflammation & NF-κB

Chronic inflammation is soil for cancer: it feeds growth signals, DNA damage, and immune suppression. The NF-κB switch inside cells is the master relay, and colitis, hepatitis, and H. pylori gastritis are the clinical proof.

Tumour-promoting inflammation (a hallmark enabling characteristic) acts through IL-6/STAT3, TNF/NF-κB, IL-1β, COX-2/PGE2, and inflammasome signalling. NF-κB (canonical IKK/IκB and non-canonical NIK/RelB) drives survival, cytokine production, and the SASP; it is constitutively active in many lymphomas (ABC-DLBCL via MYD88/CD79B, BTK-dependent) and myeloma. Aspirin reduces colorectal cancer in Lynch syndrome (CAPP2) and canakinumab reduced lung cancer incidence in CANTOS (secondary analysis), though as treatment it failed. Anti-inflammatory chemoprevention is one of the few validated mechanism-based preventions.

In one picture

A wound that never heals: the repair crews keep pouring in growth signals and clearing away rubble, and a wound that is always being rebuilt is a wound where mistakes accumulate.

Diagram

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Light up a product:
Infection, injury, obesityTNF, IL-1β, IL-6IKK → IκB degradationNF-κBIL-6 → STAT3Survival, proliferation, …BCR → BTK (lymphoma)COX-2 → PGE2activatesinhibitsdruggable target (click)hit by selected productescape route

How drugs attack it

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  • Aspirin chemoprevention in Lynch syndrome (CAPP2); NSAIDs in FAP
  • BTK inhibitors (ibrutinib, zanubrutinib) shut NF-κB in CLL/lymphoma
  • IL-6/STAT3 blockade in cachexia and CRS (tocilizumab)
  • Anti-H. pylori therapy prevents gastric cancer; HBV/HCV treatment prevents HCC

Notes

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  • Leading programmes: Karin (UCSD) on NF-κB and inflammation-driven cancer; Coussens (OHSU) on inflammation and TME; Greten (Frankfurt); CAPP2 (Burn, Newcastle).

Key papers

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Connected

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