Center of Nanomedicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.
Crit Rev Oncol Hematol. 2024 May;197:104351. doi: 10.1016/j.critrevonc.2024.104351. Epub 2024 Apr 12.
Breast cancer is potentially a lethal disease and a leading cause of death in women. Chemotherapy and radiotherapy are the most frequently used treatment options. Drug resistance in advanced breast cancer limits the therapeutic output of treatment. The leading cause of resistance in breast cancer is endocrine and hormonal imbalance, particularly in triple negative and HER2 positive breast cancers. The efflux of drugs due to p-gp's activity is another leading cause of resistance. Breast cancer resistant protein also contributes significantly. Strategies used to combat resistance include the use of nanoparticles to target drug delivery by co-delivery of chemotherapeutic drugs and genes (siRNA and miRNA) that help to down-regulate genes causing resistance. The siRNA is specific and effectively silences p-gp and other proteins causing resistance. The use of chemosensitizers is also effective in overcoming resistance. Chemo-sensitizers sensitize cancer cells to the effects of chemotherapeutic drugs. Novel anti-neoplastic agents such as antibody-drug conjugates and mesenchymal stem cells are also effective tools used to improve the therapeutic response in breast cancer. Similarly, combination of photo/thermal ablation with chemotherapy can act to overcome breast cancer resistance. In this review, we focus on the mechanism of breast cancer resistance and the nanoparticle-based strategies used to combat resistance in breast cancer.
乳腺癌是一种潜在的致命疾病，也是女性死亡的主要原因。化疗和放疗是最常用的治疗方法。晚期乳腺癌的药物耐药性限制了治疗的疗效。乳腺癌耐药的主要原因是内分泌和激素失衡，特别是在三阴性和 HER2 阳性乳腺癌中。由于 p-糖蛋白的活性导致药物外排也是耐药的另一个主要原因。乳腺癌耐药蛋白也有很大的贡献。用于对抗耐药性的策略包括使用纳米颗粒通过共递送化疗药物和基因（siRNA 和 miRNA）来靶向药物递送，这些基因有助于下调导致耐药性的基因。siRNA 是特异性的，可有效沉默 p-糖蛋白和其他导致耐药性的蛋白。使用化疗增敏剂也能有效地克服耐药性。化疗增敏剂使癌细胞对化疗药物的作用敏感。新型抗肿瘤药物，如抗体药物偶联物和间充质干细胞，也是用于提高乳腺癌治疗反应的有效工具。同样，将光/热消融与化疗相结合可以克服乳腺癌的耐药性。在这篇综述中，我们重点介绍了乳腺癌耐药的机制以及基于纳米颗粒的策略，用于对抗乳腺癌的耐药性。
