Tanespimycin with bortezomib: activity in relapsed/refractory patients with multiple myeloma.
Tanespimycin with bortezomib: activity in relapsed/refractory patients with multiple myeloma.
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DOI：
10.1111/j.1365-2141.2010.08264.x
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发表时间：
2010-08
影响因子：
6.5
通讯作者：
Anderson KC
中科院分区：
文献类型：
--
作者：
Richardson PG;Badros AZ;Jagannath S;Tarantolo S;Wolf JL;Albitar M;Berman D;Messina M;Anderson KC
坦司匹霉素（17-烯丙基氨基-17-去甲氧基格尔德霉素，17-AAG）破坏热休克蛋白90（HSP 90），HSP 90是一种对骨髓瘤生长、存活和耐药性至关重要的信号转导蛋白的关键分子伴侣。在先前的研究中，坦司匹霉素单药治疗在接受过大量预治疗的复发性/难治性多发性骨髓瘤（MM）患者中耐受性良好且有效。临床前数据显示，坦司匹霉素和硼替佐米之间具有抗肿瘤协同作用，泛素化蛋白质的细胞内积累比单独使用任何一种药物都更明显，这种作用归因于20 S蛋白酶体中胰凝乳蛋白酶活性的协同抑制。在所有1期tanespimycin研究中均观察到了HSP 70诱导，其中已对其进行了测量，有几份单独的报告表明HSP 70过表达可保护周围神经损伤。在这项II期、开放标签、多中心研究中，我们比较了1.3 mg/m2硼替佐米+三种剂量的他尼霉素：50、175和340 mg/m2治疗重度预治疗的复发性和难治性MM患者，并测量了治疗患者血浆中的HSP 70表达和蛋白酶体活性水平。由于资源原因，研究提前关闭，无法进行剂量比较。尽管如此，观察到抗肿瘤活性，有希望的反应率和周围神经病变的严重程度。
Tanespimycin (17-allylamino-17-demethoxygeldanamycin, 17-AAG) disrupts heat shock protein 90 (HSP90), a key molecular chaperone for signal transduction proteins critical to myeloma growth, survival and drug resistance. In previous studies, tanespimycin monotherapy was well tolerated and active in heavily pretreated patients with relapsed/refractory multiple myeloma (MM). Preclinical data have shown antitumour synergy between tanespimycin and bortezomib, with more pronounced intracellular accumulation of ubiquitinated proteins than either drug alone, an effect attributed to the synergistic suppression of chymotryptic activity in the 20S proteasome. HSP70 induction has been observed in all Phase 1 tanespimycin studies in which it has been measured, with several separate reports of HSP70 overexpression protecting against peripheral nerve injury. In this Phase 2, open-label multicentre study, we compared 1·3 mg/m2 bortezomib + three doses of tanespimycin: 50, 175 and 340 mg/m2 in heavily pretreated patients with relapsed and refractory MM and measured HSP70 expression and proteasome activity levels in plasma of treated patients. The study was closed prematurely for resource-based reasons, precluding dose comparison. Nonetheless, antitumour activity was observed, with promising response rates and promising severity of peripheral neuropathy.
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影响因子：
45.3
作者：
Grem, JL;Morrison, G;Wilson, RH
通讯作者：
Wilson, RH
影响因子：
11.5
作者：
Nowakowski, Grzegorz S.;McCollum, Andrea K.;Erlichman, Charles
通讯作者：
Erlichman, Charles
DOI：
10.1196/annals.1391.032
发表时间：
2007-01-01
期刊：
STRESS RESPONSES IN BIOLOGY AND MEDICINE
影响因子：
--
作者：
Brown, Ian R.
通讯作者：
Brown, Ian R.
影响因子：
45.3
作者：
Barlogie, Bart;Attal, Michel;Harousseau, Jean-Luc
通讯作者：
Harousseau, Jean-Luc
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