摘要
在肿瘤的发展和其中的表观遗传变异的参与现在已经建立。然而,睾丸癌中表观遗传改变知道的很少,特别是在铂难治性生殖细胞肿瘤。源于睾丸癌的生殖细胞,与体细胞肿瘤相比,似乎有一个独特的以更广泛的DNA甲基化为特征的表观分布。从临床标本中出现的数据表明,表观遗传畸变,特别是DNA甲基化,会导致化疗耐药和睾丸生殖细胞肿瘤临床疗效差。最近的数据表明,睾丸癌细胞,即使是那些耐铂的,都对低剂量的甲基化剂高度敏感。基于这些有前景的临床前研究,我们认为,DNA甲基化抑制剂与化疗药物的结合可能为克服睾丸癌耐药提供了一个路径,在临床上为检验这一类表观遗传学药物奠定基础和理论基础。在这个简短的回顾中,我们提供了用DNA甲基化治疗法治疗难治性睾丸癌的简短概述。
关键词: 睾丸癌、生殖细胞瘤、胚胎癌,顺铂耐药,表观遗传学,DNA甲基转移酶,地西他滨,SGI-110
图形摘要
Current Cancer Drug Targets
Title:Epigenetic Targeting of Platinum Resistant Testicular Cancer
Volume: 16 Issue: 9
Author(s): Daniel Sonnenburg, Michael J. Spinella, Costantine Albany
Affiliation:
关键词: 睾丸癌、生殖细胞瘤、胚胎癌,顺铂耐药,表观遗传学,DNA甲基转移酶,地西他滨,SGI-110
摘要: The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, little is known of the epigenetic alterations in testicular cancer and particularly in platinum refractory germ cell tumors. Germ cell derived testicular cancers, as compared to somatic tumors, appear to have a unique epigenetic profile that features more extensive DNA hypomethylation. Emerging data from clinical specimens suggest that epigenetic aberrations, especially DNA hypermethylation, can contribute to chemotherapy resistance and poor clinical outcomes in testicular germ cell tumors. Recent data indicate that testicular cancer cells, even those resistant to platinum, are highly sensitive to low doses of demethylating agents. Based on these promising preclinical studies, we suggest that DNA methylation inhibitors in combination with chemotherapeutic agents may offer a path to overcome acquired drug resistance in testicular cancer, laying the foundation and rationale for testing this class of epigenetic drugs in the clinical setting. In this mini-review we provide a brief overview of the promise of DNA methylation therapy to treat patients with refractory cancer of the testes.
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Cite this article as:
Daniel Sonnenburg, Michael J. Spinella, Costantine Albany , Epigenetic Targeting of Platinum Resistant Testicular Cancer, Current Cancer Drug Targets 2016; 16 (9) . https://dx.doi.org/10.2174/1568009616666151222150359
DOI https://dx.doi.org/10.2174/1568009616666151222150359 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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