Singhai Harshita, Raikwar Sarjana, Rathee Sunny, Jain Sanjay K
Department of Pharmaceutical Sciences, Pharmaceutics Research Projects Laboratory, Dr. Harisingh Gour Vishwavidyalaya, Sagar (M.P.), 470003, India.
Department of Pharmacy, Gyan Ganga Institute of Technology and Sciences, Jabalpur, Madhya Pradesh, 482003, India.
Curr Drug Targets. 2025;26(5):331-349. doi: 10.2174/0113894501352081241211090911.
Breast cancer remains the second most prevalent cancer among women in the United States. Despite advancements in surgical, radiological, and chemotherapeutic techniques, multidrug resistance continues to pose significant challenges in effective treatment. Combination chemotherapy has emerged as a promising approach to address these limitations, allowing multiple drugs to target malignancies via distinct mechanisms of action. Increasingly, the use of phytoconstituents alongside chemotherapeutic agents has shown promise in enhancing treatment outcomes. This combination therapy acts on key signaling pathways such as Hedgehog, Notch, Wnt/β- catenin, tyrosine kinases, and phosphatidylinositol 3-kinase (PI3K), which play critical roles in cellular proliferation, apoptosis, angiogenesis, differentiation, invasion, and metastasis. This review explores various signaling pathways involved in breast cancer progression, discusses conventional treatment methods like surgery, adjuvant radiotherapy, hormonal therapy, and chemotherapy, and highlights emerging nanocarrier-based drug delivery systems (DDS). Liposomes, dendrimers, exosomes, polymeric micelles, and nanoparticles (organic, inorganic, gold, magnetic, carbon-based, and quantum dots) are examined as innovative strategies for enhancing drug delivery efficacy. Furthermore, stimuli-responsive DDSs, including reactive oxygen species (ROS), enzyme-, and hypoxia- responsive systems, are presented as cutting-edge approaches to overcoming drug resistance. Special emphasis is placed on the co-delivery of chemotherapeutic agents and plant-based compounds, particularly in estrogen receptor-positive (ER+) breast cancer. This review aims to provide a comprehensive overview of novel combinatorial strategies and advanced nanocarriers for the effective and targeted treatment of breast cancer.
乳腺癌仍是美国女性中第二大常见癌症。尽管手术、放射和化疗技术有所进步，但多药耐药性在有效治疗方面仍然构成重大挑战。联合化疗已成为解决这些局限性的一种有前景的方法，它允许多种药物通过不同的作用机制靶向恶性肿瘤。越来越多的研究表明，将植物成分与化疗药物联合使用有望提高治疗效果。这种联合疗法作用于关键信号通路，如刺猬信号通路、Notch信号通路、Wnt/β-连环蛋白信号通路、酪氨酸激酶和磷脂酰肌醇3-激酶（PI3K），这些信号通路在细胞增殖、凋亡、血管生成、分化、侵袭和转移中起着关键作用。本文综述探讨了参与乳腺癌进展的各种信号通路，讨论了手术、辅助放疗、激素治疗和化疗等传统治疗方法，并重点介绍了新兴的基于纳米载体的药物递送系统（DDS）。脂质体、树枝状大分子、外泌体、聚合物胶束和纳米颗粒（有机、无机、金、磁性、碳基和量子点）被视为提高药物递送效率的创新策略。此外，还介绍了刺激响应性DDS，包括活性氧（ROS）、酶和缺氧响应系统，作为克服耐药性的前沿方法。特别强调了化疗药物和植物性化合物的联合递送，尤其是在雌激素受体阳性（ER+）乳腺癌中。本文综述旨在全面概述用于有效和靶向治疗乳腺癌的新型联合策略和先进纳米载体。
