Ulcerative colitis and colorectal cancer: Pathogenic insights and precision strategies for prevention and treatment

Table 1 Summary of key molecular and cellular pathways in colitis-associated colorectal cancer

Pathway/cell type	Key mediators	Biological role	Impact on tumorigenesis
IL-6/JAK/STAT3 pathway	IL-6, JAK, STAT3	Promotes epithelial proliferation and inhibits apoptosis	Facilitates CI and epithelial transformation
NF-κB signaling	NF-κB, TNF-α	Controls immune and inflammatory gene expression	Sustains pro-tumorigenic inflammation
TGF-β pathway	TGF-β, TGFBR2	Regulates epithelial growth; normally anti-proliferative	Loss or mutation promotes tumor progression
SOCS3 regulation	SOCS3	Inhibits STAT3-mediated signaling	Dysregulation leads to enhanced inflammation and carcinogenesis
MAPK/ASK1 signaling	ASK1	Mediates stress response and immune modulation	ASK1 deficiency exacerbates inflammation and susceptibility to cancer
CD4+ T helper cells	IL-17, IL-22, IL-9	Stimulate epithelial regeneration and immune activation	Promote dysplasia and tumor development
Macrophages (M1/M2)	IL-13, CCL17 (M2), TNF-α (M1)	M1: Antitumor; M2: Tumor-promoting via immunosuppression and cytokine release	High M2 infiltration is linked to poor prognosis and metastasis
Regulatory T cells	FOXP3, IL-10	Maintain immune tolerance and suppress inflammation	Dual role: Contextually antitumor or tumor-permissive
Tumor-infiltrating leukocytes	Various cytokines and chemokines	Orchestrate local immune response	Serve as prognostic markers; role depends on cellular composition
S100 family proteins	S100A9, S100A8	Mediate inflammation and immune cell recruitment	Correlated with tumor progression; potential therapeutic targeting

IL: Interleukin; JAK: Janus kinase; STAT: Signal transducer and activator of transcription; CI: Chronic inflammation; NF-κB: Nuclear factor kappa B; TNF: Tumor necrosis factor; TGF-β: Tumor growth factor-beta; TGFBR2: Transforming growth factor beta receptor 2; SOCS: Suppressor of cytokine signaling; MAPK: Mitogen-activated protein kinase; ASK: Apoptosis signal-regulating kinase; CCL: Chemokine ligand; FOXP3: Forkhead box P3.