Pro-inflammatory Oncogenic Driver
Definition: A *pro-inflammatory oncogenic driver* is a genetic or molecular alteration that simultaneously promotes malignant transformation (oncogenesis) and chronic inflammation, fostering tumor development and progression.
Key Features
- Activates inflammatory signaling pathways (e.g., NF-κB, STAT3).
- Promotes cell proliferation, survival, and immune evasion.
- Shapes the tumor microenvironment to support angiogenesis and metastasis.
- Creates a positive feedback loop between inflammation and tumor growth.
Common Examples
| Driver / Pathway | Role in Inflammation and Cancer |
|---|---|
| Mutated KRAS | Activates MAPK and NF-κB → increases pro-inflammatory cytokines. |
| MYC overexpression | Regulates inflammatory and metabolic genes in the tumor environment. |
| Constitutive NF-κB | Drives chronic inflammation and survival gene expression. |
| Activated STAT3 | Induces IL-6, VEGF, and other oncogenic inflammatory mediators. |
| TP53 loss | Impairs immune surveillance → unresolved inflammation. |
| COX-2 overexpression | Elevates prostaglandins → enhances inflammation and tumor growth. |
Clinical Relevance
- Therapeutic Targeting: These drivers are candidates for combined oncologic and anti-inflammatory therapies.
- Biomarkers: Their dual role makes them valuable prognostic or predictive biomarkers.
- Immunotherapy Modulation: Targeting these pathways may enhance immune responses against tumors.
References
- Greten, F.R., Grivennikov, S.I. (2019). Inflammation and Cancer: Triggers, Mechanisms, and Consequences. *Immunity*.
- Mantovani, A., et al. (2008). Cancer-related inflammation. *Nature*.