Recent developments in targeting carbonic anhydrase IX for cancer therapeutics.

Recent developments in targeting carbonic anhydrase IX for cancer therapeutics.
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靶向碳酸酐酶IX用于癌症治疗剂的最新发展。

DOI:
10.18632/oncotarget.422
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发表时间:
2012-01
期刊:
影响因子:
--
通讯作者:
Dedhar S
Dedhar S
中科院分区:
其他
文献类型:
--
作者:
McDonald PC;Winum JY;Supuran CT;Dedhar S

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碳酸酐酶IX(CAIX)是由来自许多肿瘤类型的癌细胞过表达的低氧诱导型酶,并且是由这些细胞调用以对抗高速率糖酵解代谢的有害作用的pH调节系统的组分。CAIX的功能是帮助产生和维持有利于肿瘤细胞生长和存活的细胞内pH(pHi),同时参与产生越来越酸性的细胞外空间,促进肿瘤细胞侵袭。使用单克隆抗体或CAIX特异性小分子抑制剂对CAIX催化活性的药理学干扰,从而破坏癌细胞的pH调节,最近已显示损害原发性肿瘤生长和转移。这些药物中有许多处于临床前或临床开发阶段,构成了癌症治疗的新的靶向策略。
Carbonic anhydrase IX (CAIX) is a hypoxia-inducible enzyme that is overexpressed by cancer cells from many tumor types, and is a component of the pH regulatory system invoked by these cells to combat the deleterious effects of a high rate of glycolytic metabolism. CAIX functions to help produce and maintain an intracellular pH (pHi) favorable for tumor cell growth and survival, while at the same time participating in the generation of an increasingly acidic extracellular space, facilitating tumor cell invasiveness. Pharmacologic interference of CAIX catalytic activity using monoclonal antibodies or CAIX-specific small molecule inhibitors, consequently disrupting pH regulation by cancer cells, has been shown recently to impair primary tumor growth and metastasis. Many of these agents are in preclinical or clinical development and constitute a novel, targeted strategy for cancer therapy.
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