Damaskos Christos, Garmpis Nikolaos, Valsami Serena, Kontos Michael, Spartalis Eleftherios, Kalampokas Theodoros, Kalampokas Emmanouil, Athanasiou Antonios, Moris Demetrios, Daskalopoulou Afrodite, Davakis Spyridon, Tsourouflis Gerasimos, Kontzoglou Konstantinos, Perrea Despina, Nikiteas Nikolaos, Dimitroulis Dimitrios
Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
N.S. Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Anticancer Res. 2017 Jan;37(1):35-46. doi: 10.21873/anticanres.11286.
With a lifetime risk estimated to be one in eight in industrialized countries, breast cancer is the most frequent type of cancer among women worldwide. Patients are often treated with anti-estrogens, but it is common that some tumors develop resistance to therapy. The causation and progression of cancer is controlled by epigenetic processes, so there is an ongoing interest in research into mechanisms, genes and signaling pathways associating carcinogenesis with epigenetic modulation of gene expression. Given the fact that histone deacetylases (HDACs) have a great impact on chromatin remodeling and epigenetics, their inhibitors have become a very interesting field of research.
This review focused on the use of HDAC inhibitors as anticancer treatment and explains the mechanisms of therapeutic effects on breast cancer. We anticipate further clinical benefits of this new class of drugs, both as single agents and in combination therapy. Molecules such as suberoylanilide hydroxamic acid, trichostatin A, suberoylbis-hydroxamic acid, panobinostat, entinostat, valproic acid, sodium butyrate, SK7041, FTY720, N-(2-hydroxyphenyl)-2-propylpentanamide, Scriptaid, YCW1, santacruzamate A and ferrocenyl have shown promising antitumor effects against breast cancer. HDAC inhibitors consists an attractive field for targeted therapy against breast cancer. Future therapeutic strategies will include combination of HDAC inhibitors and chemotherapy or other inhibitors, in order to target multiple oncogenic signaling pathways. More trials are needed.
在工业化国家,乳腺癌的终生风险估计为八分之一,是全球女性中最常见的癌症类型。患者通常接受抗雌激素治疗,但一些肿瘤对治疗产生耐药性的情况很常见。癌症的发生和进展受表观遗传过程控制,因此人们一直对研究将致癌作用与基因表达的表观遗传调控相关联的机制、基因和信号通路感兴趣。鉴于组蛋白脱乙酰酶(HDACs)对染色质重塑和表观遗传学有重大影响,其抑制剂已成为一个非常有趣的研究领域。
本综述聚焦于HDAC抑制剂作为抗癌治疗的应用,并解释其对乳腺癌的治疗作用机制。我们预期这类新药无论是作为单一药物还是联合治疗都将带来更多临床益处。诸如辛二酰苯胺异羟肟酸、曲古抑菌素A、辛二酰双异羟肟酸、帕比司他、恩替司他、丙戊酸、丁酸钠、SK7041、FTY720、N-(2-羟苯基)-2-丙基戊酰胺、司立他汀、YCW1、圣克鲁扎酯A和二茂铁基等分子已显示出对乳腺癌有可观的抗肿瘤作用。HDAC抑制剂构成了针对乳腺癌进行靶向治疗的一个有吸引力的领域。未来的治疗策略将包括HDAC抑制剂与化疗或其他抑制剂联合使用,以靶向多个致癌信号通路。还需要更多试验。