Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors.
Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors.
复制标题
DOI：
10.1586/era.10.88
复制
发表时间：
2010-07
影响因子：
3.3
通讯作者：
Bates SE
中科院分区：
文献类型：
--
作者：
Grant C;Rahman F;Piekarz R;Peer C;Frye R;Robey RW;Gardner ER;Figg WD;Bates SE
罗米地辛是一种组蛋白去乙酰化酶抑制剂（HDI），已被美国FDA批准用于治疗皮肤t细胞淋巴瘤（CTCL）。虽然HDls的活性机制有多种，包括诱导控制细胞周期的基因，胞质蛋白的乙酰化和直接诱导细胞凋亡，但罗米地辛和其他HDIs在CTCL中的活性机制尚不清楚。罗米地辛诱导持久的反应。其副作用与其他hdi相似，引起疲劳、恶心和血小板减少。CTCL人群的管理需要警惕，以防止皮肤污染物感染，并监测钾和镁，电解质在很大一部分患者中发现较低。心电图（ECG）改变是常见的，但与心肌损伤无关。当对61名参加罗米地辛II期试验的患者的分子终点进行评估时，反应与乙酰化组蛋白H3的持久性有关，这表明药物暴露对罗米地辛的有效治疗很重要。未来的研究将努力确定联合策略，以提高耐药CTCL和实体瘤的疗效，并确定反应的生物标志物，以便选择最有可能从治疗中受益的患者。
Romidepsin is a histone deacetylase inhibitor (HDI), approved by the US FDA for the treatment of cutaneous T-cell lymphoma (CTCL). Although various mechanisms have been proposed for the activity of HDls, including induction of genes controlling cell cycle, acetylation of cytoplasmic proteins and direct induction of apoptosis, the mechanism underlying activity of romidepsin and other HDIs in CTCL is not known. Romidepsin induces long-lasting responses. The side-effect profile is similar to that of other HDIs, causing fatigue, nausea and thrombocytopenia. Management of the CTCL population requires vigilence to prevent infection with skin contaminants, and monitoring of potassium and magnesium, electrolytes found to be low ina large proportion of patients. Electrocardiographic (ECG) changes are common but are not associated with myocardial damage. When molecular end points were evaluated in 61 patients enrolled on a Phase II trial with romidepsin, response was associated with persistence of acetylated histone H3, suggesting that drug exposure is important in effective therapy with romidepsin. Future studies will endeavor to identify combination strategies to increase the efficacy both in resistant CTCL and in solid tumors and to identify biomarkers of response that will allow selection of patients most likely to benefit from the therapy.
登录
查看更多内容
影响因子：
14.8
作者：
Bradner, James E.;West, Nathan;Grachan, Melissa L.;Greenberg, Edward F.;Haggarty, Stephen J.;Warnow, Tandy;Mazitschek, Ralph
通讯作者：
Mazitschek, Ralph
影响因子：
20.3
作者：
Catley, Laurence;Weisberg, Ellen;Anderson, Kenneth C.
通讯作者：
Anderson, Kenneth C.
Vorinostat与Bortezomib结合的I阶段研究，用于复发和难治性多发性骨髓瘤。
影响因子：
11.5
作者：
Badros, Ashraf;Burger, Angelika M.;Philip, Sunita;Niesvizky, Ruben;Kolla, Sarah S.;Goloubeva, Olga;Harris, Carolynn;Zwiebel, James;Wright, John J.;Espinoza-Delgado, Igor;Baer, Maria R.;Holleran, Julianne L.;Egorin, Merrill J.;Grant, Steven
通讯作者：
Grant, Steven
影响因子：
11.2
作者：
Geng, Ling;Cuneo, Kyle C.;Hallahan, Dennis E.
通讯作者：
Hallahan, Dennis E.
影响因子：
5.3
作者：
Dai, Y;Rahmani, M;Grant, S
通讯作者：
Grant, S