Ministry of Education (MOE) Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology , Tsinghua University , Beijing 100084 , P. R. China.
Tsinghua-Peking Center for Life Sciences , Beijing 100084 , P. R. China.
Biochemistry. 2020 Jan 28;59(3):240-249. doi: 10.1021/acs.biochem.9b00848. Epub 2019 Nov 4.
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.
癌症耐药性已成为当前各种治疗方法所面临的主要问题。蛋白水解靶向嵌合体（PROTACs）作为一种新颖而强大的策略，凭借其与传统抑制剂相比的独特特性，对耐药靶标具有敏感性，引起了学术界和工业界的极大关注。PROTACs 通过降解靶蛋白而不是抑制靶标来发挥作用。因此，PROTACs 可以克服各种耐药性，例如靶突变或过表达。PROTACs 已经克服了各种耐药靶标，包括 AR、ER、BTK、BET 和 BCR-ABL。尽管 PROTACs 在对抗耐药性方面取得了一些重大进展，但还需要更多的病例来证明 PROTACs 在解决耐药性障碍方面的效率，在不久的将来。
