Core Viewpoint - The study highlights the significance of gene fusions, particularly ADK fusions, in hormone receptor-positive breast cancer, suggesting they are key drivers of cancer progression and potential therapeutic targets [2][3][5]. Group 1: Gene Fusion Insights - The research presents a comprehensive landscape of gene fusions in hormone receptor-positive (HR+) breast cancer, identifying ADK fusions, such as KAT6B::ADK, as novel and recurrent driver genes [3][5]. - The KAT6B::ADK fusion gene enhances the metastatic potential of breast cancer and confers resistance to tamoxifen, a common anti-estrogen drug used in breast cancer treatment [7]. Group 2: Mechanisms and Therapeutic Implications - Mechanistically, KAT6B::ADK activates ADK kinase activity through liquid-liquid phase separation (LLPS), triggering the activation of integrated stress response signaling pathways [7]. - Organoids derived from HR+/HER2- breast cancer patients carrying KAT6B::ADK exhibit higher sensitivity to ADK inhibitors, underscoring the therapeutic potential of this fusion gene in breast cancer treatment [9].