Key regulators of sensitivity to immunomodulatory drugs in cancer treatment.
Key regulators of sensitivity to immunomodulatory drugs in cancer treatment.
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癌症治疗中免疫调节药物敏感性的关键调节因子
DOI：
10.1186/s40364-021-00297-6
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发表时间：
2021-06-05
影响因子：
11.1
通讯作者：
Gao S
中科院分区：
文献类型：
--
作者：
Wang S;Li Z;Gao S
免疫调节药物（IMiD）包括沙利度胺、来那度胺和泊马度胺，其在治疗多发性骨髓瘤（MM）、伴有染色体5 q缺失（del（5 q））的骨髓增生异常综合征（MDS）和其他血液系统恶性肿瘤中显示出显著疗效。IMiD劫持CRL 4CRBNubiquitin连接酶以靶向细胞蛋白进行泛素化和降解，这是其在具有del（5 q）的MM和MDS中的临床活性的原因。然而，内在和获得性耐药性经常限制IMiD的疗效。最近，已经做出了许多努力，探索IMiD敏感性的关键调节器，从而在理解与这类药物相关的调节网络方面取得了很大进展。本文综述了IMiD在肿瘤治疗中的作用机制，并对IMiD敏感性的关键调节因子进行了总结。此外，我们引入了全基因组CRISPR-Cas9筛选，通过该筛选可以识别IMiD敏感性的调控网络。
Immunomodulatory drugs (IMiDs) include thalidomide, lenalidomide, and pomalidomide, which have shown significant efficacy in the treatment of multiple myeloma (MM), myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) and other hematological malignancies. IMiDs hijack the CRL4CRBNubiquitin ligase to target cellular proteins for ubiquitination and degradation, which is responsible for their clinical activity in MM and MDS with del(5q). However, intrinsic and acquired resistance frequently limit the efficacy of IMiDs. Recently, many efforts have been made to explore key regulators of IMiD sensitivity, resulting in great advances in the understanding of the regulatory networks related to this class of drugs. In this review, we describe the mechanism of IMiDs in cancer treatment and summarize the key regulators of IMiD sensitivity. Furthermore, we introduce genome-wide CRISPR-Cas9 screenings, through which the regulatory networks of IMiD sensitivity could be identified.
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影响因子：
28.5
作者：
Dimopoulos M;Wang M;Maisnar V;Minarik J;Bensinger W;Mateos MV;Obreja M;Blaedel J;Moreau P
通讯作者：
Moreau P
DOI：
10.1038/nrd.2016.238
发表时间：
2017-02
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Fellmann C;Gowen BG;Lin PC;Doudna JA;Corn JE
通讯作者：
Corn JE
影响因子：
45.3
作者：
Badoux, Xavier C.;Keating, Michael J.;Ferrajoli, Alessandra
通讯作者：
Ferrajoli, Alessandra
影响因子：
4.8
作者：
Bjorklund, Chad C.;Ma, Wencai;Orlowski, Robert Z.
通讯作者：
Orlowski, Robert Z.
影响因子：
16.6
作者：
An J;Ponthier CM;Sack R;Seebacher J;Stadler MB;Donovan KA;Fischer ES
通讯作者：
Fischer ES