Alamolhodaei Nafiseh Sadat, Behravan Javad, Mosaffa Fatemeh, Karimi Gholamreza
Pharmaceutical Research Center, Pharmacy School, Mashhad University of Medical Sciences, Mashhad, Iran.
Curr Pharm Des. 2016;22(46):6946-6955. doi: 10.2174/1381612822666161102100211.
Breast cancer is the most frequent cancer in women. Despite advances in early detection and treatment, it has the second highest mortality rate after lung cancer. Around 85% of breast carcinomas are ER+; thus, antiestrogens like tamoxifen are beneficial. Although, tamoxifen is useful for many patients, a number of patients respond poorly to initial therapy or recurrence occurs in about 30% of cases, because tamoxifen resistance happens. Drug resistance remains a major clinical obstacle to successful treatment of breast cancer and more than 90% of unsuccessful treatments are because of acquired resistance and MultiDrug Resistance (MDR) is a major contributor. MicroRNAs are members of a novel class of short noncoding RNAs. Besides their various roles in gene expression, miRNAs are considered as important cancer therapeutic targets and biomarkers. Since 2005, when miRNA deregulation was first reported in breast cancer, more than 1000 reports have been published about miRNAs. Increasing number of studies showed the importance of miRNAs in antiestrogen therapy, especially on tamoxifen; thus, it is not surprising that these tiny molecules are involved in drug resistance. Due to the pivotal role of these known RNA molecules, in this review, we tried to illustrate the importance of the miRNAs as a new player in breast cancer pathogenesis. We have also focused on cancer drug resistance mechanisms highlighting the role of important oncomirs, miR 221/222, involved in cell cycle deregulation in breast cancer. The relationship between these oncomiRs with resistance to tamoxifen is also emphasized.
乳腺癌是女性中最常见的癌症。尽管在早期检测和治疗方面取得了进展，但它的死亡率在肺癌之后位居第二。大约85%的乳腺癌为雌激素受体阳性（ER+）；因此，像他莫昔芬这样的抗雌激素药物是有益的。虽然他莫昔芬对许多患者有用，但一些患者对初始治疗反应不佳，或者在约30%的病例中会复发，因为会出现他莫昔芬耐药。耐药性仍然是乳腺癌成功治疗的主要临床障碍，超过90%的治疗失败是由于获得性耐药，而多药耐药（MDR）是主要原因。微小RNA（miRNA）是一类新型的短非编码RNA成员。除了在基因表达中发挥各种作用外，miRNA还被视为重要的癌症治疗靶点和生物标志物。自2005年首次报道乳腺癌中miRNA失调以来，已经发表了1000多篇关于miRNA的报告。越来越多的研究表明miRNA在抗雌激素治疗中，尤其是对他莫昔芬治疗中的重要性；因此，这些微小分子参与耐药并不奇怪。由于这些已知RNA分子的关键作用，在本综述中，我们试图阐明miRNA作为乳腺癌发病机制中一个新角色的重要性。我们还重点关注了癌症耐药机制，突出了重要的致癌miRNA，即miR 221/222在乳腺癌细胞周期失调中的作用。还强调了这些致癌miRNA与他莫昔芬耐药之间的关系。
