MicroRNA-mediated modulation of cancer-associated fibroblasts in HER2-positive breast tumor microenvironment: a comprehensive review

Abstract

The intricate interplay within the tumor microenvironment (TME) significantly dictates the trajectory of cancer progression and therapeutic response. In HER2-positive breast cancer, a particularly aggressive subtype, cancer-associated fibroblasts (CAFs) emerge as pivotal stromal components, actively orchestrating malignant behaviors. Concurrently, microRNAs (miRNAs), small non-coding RNAs, serve as potent post-transcriptional regulators and critical mediators of intercellular communication, often encapsulated within exosomes. This review provides a comprehensive analysis of the reciprocal miRNA-mediated modulation between HER2-positive breast cancer cells and CAFs. It elucidates how tumor cell-derived miRNAs reprogram normal fibroblasts into pro-tumorigenic CAFs, and how CAF-derived miRNAs, in turn, influence HER2-positive cancer cell proliferation, invasion, metastasis, and crucially, resistance to HER2-targeted therapies. Understanding this dynamic axis reveals a self-sustaining feedback loop that drives disease advancement and therapeutic evasion. This synthesis underscores the immense potential of targeting these complex miRNA-CAF interactions as a novel strategy for diagnostic, prognostic, and therapeutic interventions, aiming to overcome the persistent challenge of resistance in HER2-positive breast cancer.