Wang Jing, Yang Muyi, Li Yu, Han Bo
Department of Pathology, The Fourth People's Hospital of Jinan, Jinan, China.
Department of Pathology, Shandong University Medical School, Jinan, China.
Drug Dev Res. 2015 Nov;76(7):368-74. doi: 10.1002/ddr.21275. Epub 2015 Aug 27.
Preclinical Research Breast cancer is the most prevalent malignancy in women with more than 1.3 million new cases every year worldwide. Chemotherapy is a critical therapeutic strategy for breast cancer, while chemoresistance remains a major obstacle to treatment success. In the past two decades, significant progress has been achieved in understanding drug resistance in breast cancer, involving drug efflux, alterations in DNA repair pathways, suppression of apoptosis as well as epithelial-mesenchymal transition, and cancer stem cells. However, more effective therapeutic targets and novel biomarkers are still urgently needed to improve the overall survival and refine the therapeutic strategy for breast cancer patients. MicroRNAs (miRNAs) play crucial roles in cellular processes, such as cell differentiation, proliferation, and apoptosis. The recent discovery of miRNAs in malignancy has provided new directions for research on mechanisms underlying response to chemotherapy. Furthermore, several studies have documented that selected miRNAs, such as miR-200c and miR-34a, may influence response to chemotherapy in several tumor types, including breast cancer. The use of miRNAs as therapeutic targets to overcome chemoresistance is currently under investigation. In this review, we summarize the roles of miRNAs in chemoresistance through multiple molecular mechanisms, and highlight the potential diagnostic and therapeutic applications of miRNAs in overcoming breast cancer chemoresistance.
临床前研究
乳腺癌是女性中最常见的恶性肿瘤,全球每年有超过130万新发病例。化疗是乳腺癌的关键治疗策略,但化疗耐药仍然是治疗成功的主要障碍。在过去二十年中,在理解乳腺癌耐药性方面取得了重大进展,涉及药物外排、DNA修复途径改变、细胞凋亡抑制以及上皮-间质转化和癌症干细胞。然而,仍迫切需要更有效的治疗靶点和新型生物标志物,以提高乳腺癌患者的总体生存率并优化治疗策略。
微小RNA(miRNA)在细胞分化、增殖和凋亡等细胞过程中发挥关键作用。最近在恶性肿瘤中发现miRNA为化疗反应机制的研究提供了新方向。此外,多项研究表明,某些miRNA,如miR-200c和miR-34a,可能影响包括乳腺癌在内的几种肿瘤类型对化疗的反应。目前正在研究将miRNA用作克服化疗耐药性的治疗靶点。在本综述中,我们总结了miRNA通过多种分子机制在化疗耐药中的作用,并强调了miRNA在克服乳腺癌化疗耐药性方面的潜在诊断和治疗应用。