Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review

Wenning Wu,1,* Yufeng He,2,3,* Chunxiang Zhang2,3 1Department of Pharmacy, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 3Nucleic Acid Medicine of Luzhou Key Laboratory, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China*These authors contributed equallyCorrespondence: Chunxiang Zhang, Email [email protected]: Breast cancer treatment has advanced substantially with the development of targeted and multimodal strategies, yet tumor heterogeneity and therapeutic resistance continue to limit long-term outcomes. This review provides a concise and critical overview of established and emerging targeted therapies, with emphasis on resistance mechanisms, innovations in drug delivery, and integrative therapeutic approaches. Established modalities, including endocrine therapy, HER2-directed antibody and antibody–drug conjugate therapies, and chemotherapy, are summarized alongside key subtype-specific challenges. Emerging targets such as PARP, CDK4/6, WBP2, and Trop2, as well as metabolic and tumor-microenvironment–oriented strategies, are evaluated for their potential to overcome resistance. Advances in immunotherapy, including checkpoint inhibitors, bispecific antibodies, and CAR-T cell therapies, are examined with attention to mechanistic rationale and limitations across breast cancer subtypes. Progress in nanotechnology-based delivery systems, exosome-mediated transport, and multimodal predictive frameworks, including miRNA regulatory networks, is further assessed for its relevance to personalized treatment. Overall, this review synthesizes current molecular insights and therapeutic innovations to inform the development of more effective and durable targeted treatments for breast cancer.Plain Language Summary: Breast cancer is not a single disease. Different people develop different tumor types, which respond in different ways to treatment. Because of this diversity, many women still face treatment resistance, relapse, or limited benefit from current therapies. We wrote this review to help readers understand how new scientific advances are reshaping breast cancer treatment and what these developments may mean for future care.In this article, we explain the major treatment approaches used today, including hormone-based therapy, HER2-targeted therapy, chemotherapy, immunotherapy, and drug–antibody combinations. We also describe important new directions, such as medicines that act on DNA repair, the cell cycle, tumor metabolism, and proteins like Trop2, WBP2, and CDK4/6. We highlight how the tumor’s surrounding environment, including immune cells, fibroblasts, blood vessels, and the extracellular matrix, can either support treatment or impede its effectiveness. We also summarize emerging tools such as nanomedicine, ultrasound-guided drug delivery, and exosome-based therapies. These technologies aim to deliver drugs more precisely and overcome resistance.Our review shows that no single therapy is enough for all patients. Instead, combining targeted drugs, immunotherapy, metabolic treatments, or advanced delivery systems may offer stronger and longer-lasting effects. We also discuss early research using prediction models and microRNA networks, which may help doctors choose the best therapy for each person.Together, these findings suggest that the future of breast cancer treatment will rely on personalized, multi-target strategies designed around the unique biology of each tumor and each patient.Keywords: breast cancer, targeted therapy, drug resistance, tumor microenvironment, nanomedicine