Targeted Therapeutics in Breast Cancer: Promise, Progress, and the Challenge of Triple-negative Subtype

Breast cancer is the most common cancer that affects women globally, with several molecular subtypes defined by hormone and growth factor receptor expression. While advances in understanding the biology of these subtypes have led to targeted therapies, aggressive forms, particularly Triple-Negative Breast Cancer (TNBC), remain challenging due to their heterogeneity and lack of approved targeted options.

This review explores current treatment approaches and emerging targeted therapies across the main breast cancer subtypes. We focus on the clinical development and translational potential of poly ADP-ribose polymerase (PARP) inhibitors, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, P13K/AKT/mTOR pathway inhibitors, histone deacetylase inhibitors, multi-target tyrosine kinase inhibitors, and immune checkpoint inhibitors.

Targeted therapies have significantly improved outcomes for patients with hormone receptor-positive and HER2-positive breast cancers, enhancing overall survival. TNBC, however, continues to pose a major challenge. Molecular subtyping offers a promising path to identify actionable targets and personalised treatment strategies. Across all subtypes, drug resistance, often driven by compensatory signalling pathways, remains a critical obstacle.

Precision medicine strategies, guided by detailed molecular profiling, are essential to optimise treatment effectiveness and overcome resistance. Thoughtfully designed combination therapies and adaptive clinical trials addressing resistance mechanisms hold great potential for improving patient outcomes.

Advances in targeted and immune-based therapies are transforming breast cancer care. Leveraging molecular insights, particularly for TNBC, is crucial to delivering personalised, clinically meaningful treatments and improving outcomes across all subtypes.