Triple negative breast cancer (TNBC) patients often acquire resistant to chemotherapy.
In the study published in Nature Communications, the authors identify the IRAK1 as the crucial driver of NF-κB-related cytokine secretion involved in TNBC metastasis and therapy resistance.
Researchers report that interleukin-1 receptor-associated kinase 1 (IRAK1) is overexpressed in a subset of breast cancers, in particular triple-negative breast cancer (TNBC), where it acts to drive aggressive growth, metastasis and acquired resistance to paclitaxel treatment.
They show that IRAK1 overexpression confers TNBC growth advantage through NF-κB-related cytokine secretion and metastatic TNBC cells exhibit gain of IRAK1 dependency, resulting in high susceptibility to genetic and pharmacologic inhibition of IRAK1.
Importantly, paclitaxel treatment induces strong IRAK1 phosphorylation, an increase in inflammatory cytokine expression, enrichment of cancer stem cells and acquired resistance to paclitaxel treatment.
Pharmacologic inhibition of IRAK1 is able to reverse paclitaxel resistance by triggering massive apoptosis at least in part through inhibiting p38-MCL1 pro-survival pathway.
The study thus demonstrates IRAK1 as a promising therapeutic target for TNBC metastasis and paclitaxel resistance.