Decoding drug resistance in breast cancer through integrative frameworks and emerging insights

Drug resistance is a key barrier to the eradication and long-term control of breast cancer. In recent years, there has been an influx of new targeted and immunotherapeutic strategies guided by prognostic biomarkers that have seen varying degrees of success in different clinical settings. However, drug resistance inevitably develops attributed to breast cancer cells that can rapidly adapt to these treatments through diverse mechanisms, including genetic mutations, epigenetic reprogramming, activation of compensatory signalling pathways, and interactions with the tumour microenvironment. As a result, both intrinsic and acquired resistance frequently emerge, driving the expansion of more aggressive subpopulations and contributing to disease relapse and metastasis. Given the dynamic and evolving nature of drug resistance, continued investigation into its underlying mechanisms is essential. This review synthesizes current knowledge of drug resistance in breast cancer and highlights integrative approaches used to study it, including multi-omic analyses, modelling of tumour heterogeneity, and evaluation of tumour–microenvironment interactions. By examining how these approaches inform the development of targeted, immune-based, and combination therapies, this review underscores their potential to improve therapeutic decision-making, refine diagnostic precision, and advance personalized oncology.