Targeting transcriptional regulators for treatment of anaplastic thyroid cancer  

作　　者：Woo Kyung Lee Sheue-Yann Cheng 

机构地区：[1]Laboratory of Molecular Biology,Center for Cancer Research,National Cancer Institute,National Institutes of Health,Bethesda,MD 20892,USA

出　　处：《Journal of Cancer Metastasis and Treatment》2021年第1期381-398,共18页癌症转移与治疗（英文版）

基　　金：supported by the Intramural Research Program of the Center for Cancer Research;National Cancer Institute,National Institutes of Health(ZIA BC 011191).

摘　　要：Dysregulation of genes perpetuates cancer progression.During carcinogenesis,cancer cells acquire dependency of aberrant transcriptional programs(known as“transcription addiction”)to meet the high demands for uncontrolled proliferation.The needs for particular transcription programs for cancer growth could be cancer-type-selective.The dependencies of certain transcription regulators could be exploited for therapeutic benefits.Anaplastic thyroid cancer(ATC)is an extremely aggressive human cancer for which new treatment modalities are urgently needed.Its resistance to conventional treatments and the lack of therapeutic options for improving survival might have been attributed to extensive genetic heterogeneity due to subsequent evolving genetic alterations and clonal selections during carcinogenesis.Despite this genetic complexity,mounting evidence has revealed a characteristic transcriptional addiction of ATC cells resulting in evolving diverse oncogenic signaling for cancer cell survival.The transcriptional addiction has presented a huge challenge for effective targeting as shown by the failure of previous targeted therapies.However,an emerging notion is that many different oncogenic signaling pathways activated by multiple upstream driver mutations might ultimately converge on the transcriptional responses,which would provide an opportunity to target transcriptional regulators for treatment of ATC.Here,we review the current understanding of how genetic alterations in cancer distorted the transcription program,leading to acquisition of transcriptional addiction.We also highlight recent findings from studies aiming to exploit the opportunity for targeting transcription regulators as potential therapeutics for ATC.

关 键 词：Transcriptional addiction TRANSCRIPTION oncogene addiction cancer stem cell thyroid hormone receptors steroid receptor coactivators BET inhibitor anaplastic thyroid cancer 

分 类 号：R73[医药卫生—肿瘤]