Breast cancer is the leading cause of cancer death among women. While traditional receptor stratification (ER, PR, HER2) guides effective therapies, triple-negative breast cancer (TNBC) lacks these targets, resulting in resistance and high recurrence rates.
The tumor microenvironment (TME) drives progression via interleukin-1 (IL-1) signaling through the IL-1 receptor accessory protein (IL1RAP).
This study reveals significant IL1RAP upregulation in TNBC, correlating with poor outcomes, cancer-associated fibroblasts, and myeloid cells. Mechanistically, IL-1 induces inflammation and synergizes with the Oncostatin M (OSM) axis. Experimentally, IL1RAP blockade reduced cell viability and invasion in vitro, impaired tumor growth in ovo, and slowed regrowth in vivo.
Clinical trial analyses showed that IL1RAP inhibition modulated basal cytokines. RNA-seq of pre-treatment samples (n=43) identified inflammatory gene signatures linked to therapeutic response. Post-treatment, IL1RAP blockade decreased circulating OSM, reduced P-STAT3 expression, and downregulated key inflammatory genes.
Altogether, IL1RAP regulates TNBC inflammatory networks, offering a promising therapeutic target with strong clinical rationale.
TBD