Nelson William G, Yegnasubramanian Srinivasan, Agoston Agoston T, Bastian Patrick J, Lee Byron H, Nakayama Masashi, De Marzo Angelo M
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Brady Urological Institute, Baltimore, MD 21231, USA.
Front Biosci. 2007 May 1;12:4254-66. doi: 10.2741/2385.
Human prostatic carcinogenesis is characterized by the accumulation of both genetic and epigenetic alterations. The epigenetic changes appear earlier and more consistently, and because the DNA sequence remains intact, may be therapeutically reversible. The mechanism(s) by which epigenetic changes appear during the pathogenesis of prostate cancer have not been established. Nonetheless, new methods for the detection of abnormal DNA methylation, a molecular biomarker of epigenetic alterations, are poised to provide clinical tests potentially useful for prostate cancer detection and diagnosis. In addition, new drugs targeting DNA methyltransferases and other enzymes involved in the maintenance of chromatic structure have been introduced into clinical trials for the treatment of advanced prostate cancers. If sufficiently safe strategies for chromatin modulation can be discovered and developed, epigenetic alterations may become rational targets for both prostate cancer prevention and prostate cancer treatment.
人类前列腺癌发生的特征是遗传和表观遗传改变的积累。表观遗传变化出现得更早且更具一致性,并且由于DNA序列保持完整,可能在治疗上是可逆的。前列腺癌发病过程中表观遗传变化出现的机制尚未明确。尽管如此,检测异常DNA甲基化(表观遗传改变的一种分子生物标志物)的新方法有望提供对前列腺癌检测和诊断可能有用的临床试验。此外,针对DNA甲基转移酶和其他参与染色质结构维持的酶的新药已被引入晚期前列腺癌治疗的临床试验。如果能够发现和开发出足够安全的染色质调节策略,表观遗传改变可能成为前列腺癌预防和治疗的合理靶点。