报告摘要：

Loss of responsiveness to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Therefore, the research in my lab focuses on the discovery of context-specific transcriptional network among transcription factors, epigenetic programs and signaling pathways in transcriptional control. We aim to understand how the abnormal network leads to aberrant gene expression and ultimately contributes to therapeutic resistance. One of the epigenetic enzymes, which has been demonstrated to play an important role in cancer progression, is called EZH2, the enhancer of zeste homolog 2. EZH2 is a histone methyltransferase that catalyzes methylation of lysine 27 on histone H3. It is also shown to directly interact with DNA methyltransferases and functionally govern DNA methylation, centering EZH2 at a pivotal position linking two critical epigenetic programs. Our work discovered that EZH2 confers hormone therapy resistance in prostate and breast cancer by interaction with the master transcription factors, such as the androgen receptor (AR) and the estrogen receptor a (ERa). It regulates the transcriptional activities of the nuclear receptors, and the cooperation leads to transcriptional programs that dictate drug response of cancer cells. Selective small-molecule inhibitors that disrupt EZH2 enzymatic activity blocked the growth of resistant xenograft tumors in vivo. In summary, our work provides several novel therapeutic strategies to overcome therapy resistance in advanced cancer by targeting particular epigenetic programs for the concerted blockade of resistance-driving axes.

报告人简介：许可欣，圣安东尼奥健康中心分子医学系助理教授