ADAR1-mediated RNA editing in breast cancer: molecular mechanisms and therapeutic implications

Breast cancer (BC) continues to be among the most widespread and clinically demanding cancers globally, resulting in significant illness and death, even with progress in early detection and treatment approaches. Traditional therapeutic modalities, including surgery, chemotherapy, and targeted therapies, often fail in the face of drug resistance, metastasis, and the invasion. Consequently, a pressing demand exists for new biomarkers and treatment approaches to enhance clinical results. A recent area of focus in cancer research is RNA editing, particularly the role of Adenosine deaminase acting on RNA1 (ADAR1) which operates as an RNA editing enzyme that catalyzes adenosine-to-inosine conversion within double-stranded RNA substrates. This process affects gene expression and various cellular functions including RNA stability, splicing, and translation. Recent studies have highlighted the important function of ADAR1 editing in several types of cancer, including breast cancer, by regulating key pathways that are critical to tumor development, proliferation, and therapeutic resistance. This review aims to inspire further research into ADAR1-mediated mechanisms, offering new perspectives to overcome therapeutic resistance and improve clinical outcomes. This review systematically examines the multifaceted roles of ADAR1 in breast cancer progression, with a focus on its upstream regulators and downstream effects on critical pathways. Our analysis not only consolidates current understanding of ADAR1's regulatory networks, but also pointed out the current problems with ADAR1 in breast cancer research. What's more, we also proposed innovative strategies such as ADAR1 inhibitors to advance precision medicine in breast cancer.