Garmpis Nikolaos, Damaskos Christos, Garmpi Anna, Dimitroulis Dimitrios, Spartalis Eleftherios, Margonis Georgios-Antonios, Schizas Dimitrios, Deskou Irini, Doula Chrysoula, Magkouti Eleni, Andreatos Nikolaos, Antoniou Efstathios A, Nonni Afroditi, Kontzoglou Konstantinos, Mantas Dimitrios
Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Anticancer Res. 2017 Oct;37(10):5355-5362. doi: 10.21873/anticanres.11961.
BACKGROUND/AIM: Malignant melanoma is the most aggressive type of skin cancer, with increasing frequency and mortality. Melanoma is characterized by rapid proliferation and metastases. Malignant transformation of normal melanocytes is associated with imbalance between oncogenes' action and tumor suppressor genes. Mutations or inactivation of these genes plays an important role in the pathogenesis of malignant melanoma. Many target-specific agents improved progression-free survival but unfortunately metastatic melanoma remains incurable, so new therapeutic strategies are needed. The balance of histones' acetylation affects cell cycle progression, differentiation and apoptosis. Histone deacetylases (HDAC) are associated with different types of cancer. Histone deacetylase inhibitors (HDACI) are enzymes that inhibit the action of HDAC, resulting in block of tumor cell proliferation. A small number of these enzymes has been studied regarding their anticancer effects in melanoma. The purpose of this article was to review the therapeutic effect of HDACI against malignant melanoma, enlightening the molecular mechanisms of their action.
The MEDLINE database was used. The keywords/ phrases were; HDACI, melanoma, targeted therapies for melanoma. Our final conclusions were based on studies that didn't refer solely to melanoma due to their wider experimental data. Thirty-two articles were selected from the total number of the search's results. Only English articles published until March 2017 were used.
Molecules, such as valproid acid (VPA), LBH589, LAQ824 (dacinostat), vorinostat, tubacin, sirtinol and tx-527, suberoyl bis-hydroxamic acid (SBHA), depsipeptide and Trichostatin A (TSA) have shown promising antineoplastic effects against melanoma.
HDACI represent a promising agent for targeted therapy. More trials are required.
背景/目的：恶性黑色素瘤是最具侵袭性的皮肤癌类型，其发病率和死亡率呈上升趋势。黑色素瘤的特征是快速增殖和转移。正常黑素细胞的恶性转化与癌基因作用和肿瘤抑制基因之间的失衡有关。这些基因的突变或失活在恶性黑色素瘤的发病机制中起重要作用。许多靶向特异性药物改善了无进展生存期，但不幸的是转移性黑色素瘤仍然无法治愈，因此需要新的治疗策略。组蛋白乙酰化的平衡影响细胞周期进程、分化和凋亡。组蛋白脱乙酰酶（HDAC）与不同类型的癌症有关。组蛋白脱乙酰酶抑制剂（HDACI）是抑制HDAC作用的酶，导致肿瘤细胞增殖受阻。已经对其中少数几种酶在黑色素瘤中的抗癌作用进行了研究。本文的目的是综述HDACI对恶性黑色素瘤的治疗作用，阐明其作用的分子机制。
使用MEDLINE数据库。关键词/短语为：HDACI、黑色素瘤、黑色素瘤的靶向治疗。我们的最终结论基于那些由于实验数据更广泛而并非仅涉及黑色素瘤的研究。从搜索结果总数中选出32篇文章。仅使用截至2017年3月发表的英文文章。
丙戊酸（VPA）、LBH589、LAQ824（西达本胺）、伏立诺他、tubacin、sirtinol和tx-527、辛二酰双羟肟酸（SBHA）、缩肽和曲古抑菌素A（TSA）等分子已显示出对黑色素瘤有良好的抗肿瘤作用。
HDACI是一种有前景的靶向治疗药物。需要更多的试验。
