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利用拷贝数改变鉴定膀胱癌新的治疗靶点。

Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma.

机构信息

School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.

Medical Genetics Laboratory, San Gerardo Hospital, 20900 Monza, Italy.

出版信息

Int J Mol Sci. 2016 Feb 24;17(3):271. doi: 10.3390/ijms17030271.

Abstract

Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs). MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH) results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs) present in biopsies and retained in the corresponding cancer stem cell (CSC) subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.

摘要

膀胱癌是全球第九大常见恶性肿瘤。它的特征是存在两种不同的临床和预后亚型:非肌肉浸润性膀胱癌(NMIBC)和肌肉浸润性膀胱癌(MIBC)。MIBC 预后不良,常见转移进展。尽管知识有所进步,但近年来治疗并没有显著进展,缺乏新的治疗靶点。由于目前治疗选择的局限性,更大的挑战将是确定用于临床应用的生物标志物。出于这个原因,我们将我们的阵列比较基因组杂交 (array-CGH) 结果与文献中报道的浸润性膀胱癌进行了比较,特别是我们专注于评估活检中存在的拷贝数改变 (CNAs) 并保留在相应的癌症干细胞 (CSC) 亚群中,这些亚群应该是治疗的主要目标。根据我们的数据,CCNE1、MYC、MDM2 和 PPARG 基因可能是膀胱癌 CSC 亚群的有趣治疗靶点。令人惊讶的是,HER2 拷贝数增加不会保留在膀胱 CSCs 中,使基因靶向治疗不如其他治疗方法有趣。这些结果为膀胱癌治疗的进一步研究提供了宝贵的建议;然而,这些结果的临床重要性尚待探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07aa/4813135/90bc26add486/ijms-17-00271-g001.jpg

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本文引用的文献

1
Invasive Bladder Cancer: Genomic Insights and Therapeutic Promise.
Clin Cancer Res. 2015 Oct 15;21(20):4514-24. doi: 10.1158/1078-0432.CCR-14-1215.
2
A Modeling Approach to Explain Mutually Exclusive and Co-Occurring Genetic Alterations in Bladder Tumorigenesis.
Cancer Res. 2015 Oct 1;75(19):4042-52. doi: 10.1158/0008-5472.CAN-15-0602. Epub 2015 Aug 3.
3
Tumour-suppressive microRNA-144-5p directly targets CCNE1/2 as potential prognostic markers in bladder cancer.
Br J Cancer. 2015 Jul 14;113(2):282-9. doi: 10.1038/bjc.2015.195. Epub 2015 Jun 9.
4
Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer.
Virchows Arch. 2015 Jun;466(6):703-10. doi: 10.1007/s00428-015-1729-4. Epub 2015 Mar 26.
5
HER2 as a target in invasive urothelial carcinoma.
Cancer Med. 2015 Jun;4(6):844-52. doi: 10.1002/cam4.432. Epub 2015 Feb 26.
8
Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.
Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.
10
Comprehensive molecular characterization of urothelial bladder carcinoma.
Nature. 2014 Mar 20;507(7492):315-22. doi: 10.1038/nature12965. Epub 2014 Jan 29.

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