PROTACs as Potential Therapeutic Agents for Cancer Drug Resistance
PROTACs as Potential Therapeutic Agents for Cancer Drug Resistance
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DOI：
10.1021/acs.biochem.9b00848
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发表时间：
2020-01-28
期刊：
影响因子：
2.9
通讯作者：
Rao, Yu
中科院分区：
文献类型：
--
作者：
Sun, Xiuyun;Rao, Yu
肿瘤耐药已成为目前临床治疗中面临的主要问题。蛋白水解靶向嵌合体（Proteolysis targeting chimeras，PROTACs）作为一种新型的、强有力的药物靶向策略，凭借其与传统抑制剂相比所具有的独特特性，对耐药靶点的敏感性，引起了学术界和工业界的广泛关注。PROTAC通过降解靶蛋白而不是抑制靶来发挥其功能。因此，PROTAC可以通过靶向突变或过表达等方式克服不同类型的抗性。PROTAC已经克服了AR、ER、BTK、BET和BCR-ABL等多种耐药靶点，虽然PROTAC在抗耐药方面取得了一些显著进展，但在不久的将来还需要更多的病例来证明PROTAC在解决耐药障碍方面的有效性。
Cancer drug resistance has become the major problem facing current clinical treatment via different kinds of therapies. Proteolysis targeting chimeras (PROTACs) as a novel and powerful strategy have attracted a great deal of attention both from academia and from industry for their sensitivity to drug-resistant targets relying on their unique characteristics compared to those of traditional inhibitors. PROTACs exert their function by degrading the target protein instead of inhibiting targets. Thus, different kinds of resistance could be conquered by PROTACs such as target mutation or overexpression. Various resistant targets have been overcome by PROTACs, including AR, ER, BTK, BET, and BCR-ABL. Though PROTACs have achieved some significant advances in combating drug resistance, more cases are needed to prove the efficiency of PROTACs in addressing the hurdle of resistance in the near future.