Rational combination strategies to enhance venetoclax activity and overcome resistance in hematologic malignancies.
Rational combination strategies to enhance venetoclax activity and overcome resistance in hematologic malignancies.
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DOI：
10.1080/10428194.2017.1366999
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发表时间：
2018-06
影响因子：
2.6
通讯作者：
Grant S
中科院分区：
文献类型：
--
作者：
Grant S
维奈托克（ABT-199）是一种Bcl-2特异性BH 3模拟物，在CLL的某些亚型以及其他几种血液恶性肿瘤中显示出显著的前景。与基本上所有靶向药物的情况一样，通常会对该药物产生固有或获得性耐药性，这促使人们寻找能够规避这一问题的新策略。应对这一挑战的合理方法包括合理的组合策略，旨在禁用预先存在的或诱导的代偿性生存途径。这些策略中的许多涉及Mcl-1的下调，Mcl-1是一种促生存Bcl-2家族成员，其不被维奈托克靶向，并且通常赋予对该药剂的抗性。鉴于在淋巴和骨髓恶性肿瘤中涉及维奈托克的令人鼓舞的临床结果，在不久的将来，这种联合方法可能会被纳入多种血液恶性肿瘤的治疗手段。
Venetoclax (ABT-199) is a Bcl-2-specific BH3-mimetic that has shown significant promise in certain subtypes of CLL as well as in several other hematologic malignancies. As in the case of essentially all targeted agents, intrinsic or acquired resistance to this agent generally occurs, prompting the search for new strategies capable of circumventing this problem. A logical approach to this challenge involves rational combination strategies designed to disable preexisting or induced compensatory survival pathways. Many of these strategies involve downregulation of Mcl-1, a pro-survival Bcl-2 family member that is not targeted by venetoclax, and which often confers resistance to this agent. Given encouraging clinical results involving venetoclax in both lymphoid and myeloid malignancies, it is likely that such combination approaches will be incorporated into the therapeutic armamentarium for multiple hematologic malignancies in the near future.
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影响因子：
11.2
作者：
Chen S;Dai Y;Pei XY;Myers J;Wang L;Kramer LB;Garnett M;Schwartz DM;Su F;Simmons GL;Richey JD;Larsen DG;Dent P;Orlowski RZ;Grant S
通讯作者：
Grant S
影响因子：
--
作者：
Bodo J;Zhao X;Durkin L;Souers AJ;Phillips DC;Smith MR;Hsi ED
通讯作者：
Hsi ED
影响因子：
50.3
作者：
Certo, Michael;Moore, Victoria Del Gaizo;Letai, Anthony
通讯作者：
Letai, Anthony
DOI：
10.1158/1078-0432.ccr-14-2809
发表时间：
2015-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cervantes-Gomez F;Lamothe B;Woyach JA;Wierda WG;Keating MJ;Balakrishnan K;Gandhi V
通讯作者：
Gandhi V
影响因子：
2.6
作者：
Bose P;Gandhi V;Konopleva M
通讯作者：
Konopleva M