Epigenetics in acute promyelocytic leukaemia pathogenesis and treatment response: a TRAnsition to targeted therapies.
Epigenetics in acute promyelocytic leukaemia pathogenesis and treatment response: a TRAnsition to targeted therapies.
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DOI：
10.1038/bjc.2014.374
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发表时间：
2015-02-03
影响因子：
8.8
通讯作者：
So, C. W. E.
中科院分区：
文献类型：
--
作者：
Arteaga, M. F.;Mikesch, J-H;Fung, T-K;So, C. W. E.
关键词：
转录失调在大量癌症中起着关键作用，并且成功靶向维持疾病的致癌转录因子一直是该领域的圣杯。由编码视黄酸受体α融合体的嵌合转录因子驱动的急性早幼粒细胞白血病（APL）是靶向癌症治疗的范例，其中全反式视黄酸（ATRA）治疗的应用已经显著地将这种高度致命的癌症转变为高度可管理的疾病。使用ATRA联合三氧化二砷的靶向治疗所产生的极高的完全缓解率可能能够最大限度地减少甚至完全消除APL中高毒性化疗药物的使用。在这篇文章中，我们将回顾这些靶向治疗APL的分子基础和即将面临的挑战，并讨论我们对表观遗传学基础ATRA反应及其潜在用途的理解的最新进展，以进一步改善治疗反应和克服耐药性。
Transcriptional deregulation plays a key role in a large array of cancers, and successful targeting of oncogenic transcription factors that sustain diseases has been a holy grail in the field. Acute promyelocytic leukaemia (APL) driven by chimeric transcription factors encoding retinoic acid receptor alpha fusions is the paradigm of targeted cancer therapy, in which the application of all-trans retinoic acid (ATRA) treatments have markedly transformed this highly fatal cancer to a highly manageable disease. The extremely high complete remission rate resulted from targeted therapies using ATRA in combination with arsenic trioxide will likely be able to minimise or even totally eliminate the use of highly toxic chemotherapeutic agents in APL. In this article, we will review the molecular basis and the upcoming challenges of these targeted therapies in APL, and discuss the recent advance in our understanding of epigenetics underlying ATRA response and their potential use to further improve treatment response and overcome resistance.
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