Drug resistance in breast cancer: Mechanisms and strategies for management

Abstract

Therapeutic resistance remains a significant challenge in breast cancer treatment, often driven by factors such as genetic mutations, dysregulation of receptors and signaling pathways, alterations in drug metabolism and transport, cellular heterogeneity, and modifications in the tumor microenvironment. As a highly heterogeneous and complex disease, breast cancer exhibits distinct molecular and histopathological characteristics, necessitating tailored therapeutic approaches. This article reviews recent advancements in understanding therapy resistance across four major subtypes — Luminal A, Luminal B, HER2-enriched, and triple-negative breast cancer (TNBC) — and explores potential strategies to overcome resistance, providing insights into developing novel therapeutic interventions. Notably, TNBC patients have limited treatment options, with chemotherapy remaining the standard approach and immunotherapy emerging as an adjunct strategy. We concisely overview key mechanisms contributing to therapy resistance and discuss innovative therapeutic strategies, including combination regimens, molecularly targeted therapies, photodynamic therapy, and ferroptosis-inducing treatments. Additionally, we highlight recent advancements in multi-omics data integration and artificial intelligence-driven approaches in breast cancer research. Future efforts should focus on refining predictive models, optimizing combination therapies, and leveraging artificial intelligence to enhance treatment efficacy, ultimately overcoming resistance and improving long-term outcomes for breast cancer patients.