Huffman Kenneth, Martinez Elisabeth D
Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center , Dallas, TX , USA.
Front Oncol. 2013 Sep 9;3:235. doi: 10.3389/fonc.2013.00235.
Treatment options for lung cancer patients have been generally limited to standard therapies or targeted interventions which involve a small number of known mutations. Although the targeted therapies are initially successful, they most often result in drug resistance, relapse, and mortality. We now know that the complexity of lung cancer comes not only from genomic changes, but also from aberrant epigenetic regulatory events. Epigenetic therapies have shown promise as single agents in the treatment of hematological malignancies but have yet to meet this expectation in solid tumors thus fostering researchers to pursue new approaches in the development and use of epigenetic interventions. Here, we review some recent pre-clinical findings involving the use of drugs targeting histone modifying enzymes both as single agents and as co-therapies against lung cancer. A greater understanding of the impact of these epigenetic compounds in lung cancer signaling is needed and further evaluation in vivo is warranted in several cases based on the pre-clinical activity of a subset of compounds discussed in this review, including drugs co-targeting HDACs and EGF receptor, targeting Brd4 and targeting Jumonji histone demethylases.
肺癌患者的治疗选择通常局限于标准疗法或针对少数已知突变的靶向干预措施。尽管靶向疗法最初取得了成功，但它们大多会导致耐药性、复发和死亡。我们现在知道，肺癌的复杂性不仅源于基因组变化，还源于异常的表观遗传调控事件。表观遗传疗法作为单一药物在血液系统恶性肿瘤的治疗中显示出了前景，但在实体瘤中尚未达到这一预期，因此促使研究人员在表观遗传干预的开发和应用中寻求新方法。在这里，我们回顾了一些最近的临床前研究结果，这些研究涉及使用靶向组蛋白修饰酶的药物，既作为单一药物，也作为针对肺癌的联合疗法。需要更深入地了解这些表观遗传化合物在肺癌信号传导中的影响，并且基于本综述中讨论的一部分化合物的临床前活性，在几种情况下进行进一步的体内评估是有必要的，这些化合物包括共同靶向HDACs和表皮生长因子受体的药物、靶向Brd4的药物以及靶向Jumonji组蛋白去甲基化酶的药物。
