From challenge to solution: Perspectives on AI-powered multi-omics in tackling CDK4/6 inhibitor resistance in breast cancer

Currently, three CDK4/6 inhibitors (CDK4/6i) have been approved globally in clinical practice for combination with endocrine therapy as first-line treatment for advanced or metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 − ) breast cancer. The advent of CDK4/6i has significantly improved the survival rates of patients with breast cancer. However, once resistance to CDK4/6i emerges, follow-up treatment options are limited. Therefore, there is a growing demand for biomarkers to detect intrinsic or acquired resistance and for effective subsequent therapies. Recent advances in artificial intelligence (AI) and multi-omics data have enabled significant breakthroughs in biomarker prediction and drug development, advancing personalized medicine. This review synthesizes the primary mechanisms of CDK4/6i resistance in breast cancer and explores the current applications and prospects of integrating AI with multi-omics to overcome these challenges and advance personalized therapeutic strategies.