Chen Yinnan, Zhang Yanmin
School of Molecular Sciences Arizona State University Tempe AZ 85287 USA.
School of Pharmacy Health Science Center Xi'an Jiaotong University Xi'an Shaanxi Province 710061 P. R. China.
Adv Sci (Weinh). 2018 Apr 15;5(6):1700964. doi: 10.1002/advs.201700964. eCollection 2018 Jun.
Clinical evidence indicates that drug resistance is a great obstacle in breast cancer therapy. It renders the disease uncontrollable and causes high mortality. Multiple mechanisms contribute to the development of drug resistance, but the underlying cause is usually a shift in the genetic composition of tumor cells. It is increasingly feasible to engineer the genome with the clustered regularly interspaced short palindromic repeats (CRISPR)/associated (Cas)9 technology recently developed, which might be advantageous in overcoming drug resistance. This article discusses how the CRISPR/Cas9 system might revert resistance gene mutations and identify potential resistance targets in drug-resistant breast cancer. In addition, the challenges that impede the clinical applicability of this technology and highlight the CRISPR/Cas9 systems are presented. The CRISPR/Cas9 system is poised to play an important role in preventing drug resistance in breast cancer therapy and will become an essential tool for personalized medicine.
临床证据表明,耐药性是乳腺癌治疗中的一个巨大障碍。它使疾病难以控制,并导致高死亡率。多种机制促成了耐药性的发展,但其根本原因通常是肿瘤细胞基因组成的改变。利用最近开发的成簇规律间隔短回文重复序列(CRISPR)/相关蛋白9(Cas)9技术对基因组进行工程改造越来越可行,这在克服耐药性方面可能具有优势。本文讨论了CRISPR/Cas9系统如何逆转耐药基因突变,并在耐药性乳腺癌中识别潜在的耐药靶点。此外,还介绍了阻碍该技术临床应用的挑战,并强调了CRISPR/Cas9系统。CRISPR/Cas9系统有望在预防乳腺癌治疗中的耐药性方面发挥重要作用,并将成为个性化医疗的重要工具。