Receptor for advanced glycation end-product
RAGE (receptor for advanced glycation end-product) is thought to be associated with metastasis and poor prognosis of various types of cancer.
Cancer — Chronic Inflammation, Metastatic Signaling, and Therapy Resistance
Frequently upregulated (expression and/or activity) in tumors and surrounding stroma.
Core Oncogenic Programs Driven by RAGE
a. Chronic inflammation
-Sustained NF-κB activation
-Autocrine loops that perpetuate cytokine and chemokine production
b. Proliferation and survival
-Activation of MAPK/ERK and PI3K–AKT pathways
-Resistance to apoptosis under stress
c. Invasion and metastasis
-Induction of EMT-associated programs
-Matrix remodeling and enhanced motility
d. Angiogenesis
-Upregulation of pro-angiogenic factors in hypoxic niches
Therapeutic Implications
-Direct targeting: blocking RAGE or key ligand interactions can dampen chronic inflammation and invasion (conceptually attractive; clinical translation ongoing).
-Combination logic: RAGE pathway inhibition may sensitize tumors to chemotherapy, radiation, or immunotherapy by reducing stress-adaptive signaling.
-Biomarker role: elevated RAGE/ligand signatures can indicate inflammation-driven disease states.
RAGE is used as a clinical biomarker for inflammation state.
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