BioScreening Technology Group, Leeds Institutes of Molecular Medicine, University of Leeds, Leeds, UK.
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Breast Cancer (Dove Med Press). 2014 Jan 10;6:1-13. doi: 10.2147/BCTT.S37638. eCollection 2014.
Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. By understanding the molecular mechanisms behind multidrug-resistant breast cancer, new treatments may be developed. Here we review the recent advances in this understanding, emphasizing the common mechanisms underlying resistance to both targeted therapies, notably tamoxifen and trastuzumab, and traditional chemotherapies. We focus primarily on three molecular mechanisms, the phosphatidylinositide 3-kinase/Akt pathway, the role of microRNAs in gene silencing, and epigenetic alterations affecting gene expression, and discuss how these mechanisms can interact in multidrug resistance. The development of therapeutics targeting these mechanisms is also addressed.
乳腺癌是全世界女性最常见的癌症,而对当前治疗方法的耐药性,通常是同时发生的,这是一个日益严峻的临床挑战。通过了解多药耐药性乳腺癌背后的分子机制,可能会开发出新的治疗方法。在这里,我们综述了这方面的最新进展,强调了靶向治疗(特别是他莫昔芬和曲妥珠单抗)和传统化疗耐药的共同机制。我们主要关注三个分子机制:磷脂酰肌醇 3-激酶/蛋白激酶 B 通路、微小 RNA 在基因沉默中的作用以及影响基因表达的表观遗传改变,并讨论了这些机制如何在多药耐药中相互作用。还讨论了针对这些机制的治疗方法的开发。