A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care.
A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care.
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DOI：
10.18632/oncotarget.969
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Halatsch ME
中科院分区：
文献类型：
--
作者：
Kast RE;Boockvar JA;Brüning A;Cappello F;Chang WW;Cvek B;Dou QP;Duenas-Gonzalez A;Efferth T;Focosi D;Ghaffari SH;Karpel-Massler G;Ketola K;Khoshnevisan A;Keizman D;Magné N;Marosi C;McDonald K;Muñoz M;Paranjpe A;Pourgholami MH;Sardi I;Sella A;Srivenugopal KS;Tuccori M;Wang W;Wirtz CR;Halatsch ME
为了改善复发的胶质母细胞瘤的预后，我们开发了一种基于药物组合的治疗方案，这些药物传统上不被认为是细胞毒性化疗药物，但具有良好的耐受性，并且已经上市并用于其他非癌症适应症。重点是添加符合这些标准的药物：a)具有良好的药理学特征，b)增加患者副作用负担的可能性很低，c)有证据表明干扰了公认的、特征良好的胶质母细胞瘤的促进生长因素，以及d)协调一致，因为整体具有针对胶质母细胞瘤生长的关键生物学特征的协同活动的合理可能性。我们发现了9种符合这些标准的药物，并建议将它们添加到持续小剂量替莫唑胺中，替莫唑胺目前是一种被接受的复发性胶质母细胞瘤治疗方法，用于采用Stupp方案进行初步治疗后复发的患者。这九种辅助药物方案，协同破坏生存途径，CUSP9，然后分别是阿替普特、青蒿琥酯、金诺芬、卡托普利、葡萄糖酸铜、双硫仑、酮康唑、奈非那韦、舍曲林，要加入替莫唑胺的持续小剂量。我们依次讨论每种药物和使用的具体原理--每种药物如何预期延缓胶质母细胞瘤的生长并破坏替莫唑胺治疗期间进行的胶质母细胞瘤的代偿机制。回顾了药物相互作用的风险，以及为什么我们相信这种药物组合将提高生活质量和总体存活率。
To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
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影响因子：
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