Alternative approaches to target Myc for cancer treatment.
Alternative approaches to target Myc for cancer treatment.
复制标题
DOI：
10.1038/s41392-021-00500-y
复制
发表时间：
2021-03-10
影响因子：
39.3
通讯作者：
Huang W
中科院分区：
文献类型：
--
作者：
Wang C;Zhang J;Yin J;Gan Y;Xu S;Gu Y;Huang W
Myc原癌基因家族由三个成员组成：C-MYC、MYCN和MYCL，分别编码转录因子c-Myc（以下简称Myc）、N-Myc和L-Myc。 Myc 蛋白协调多种生理过程，包括细胞增殖、分化、存活和凋亡。 Myc 调节约 15% 的整体转录组，其解除调节会重新连接肿瘤细胞内的细胞信号模块，从而获得选择性优势。 Myc 失调发生在 > 70% 的人类癌症中，并且与不良预后相关；因此，几十年来，过度活化的 Myc 癌蛋白一直被认为是理想的药物靶点。然而，目前还没有特定的药物可以直接靶向Myc，主要是因为它的“不可成药”特性：缺乏常规小分子结合的酶口袋；由于 Myc 的主要细胞核定位，抗体无法接近。尽管过去几十年来，针对 Myc 的话题已得到积极的回顾，但该领域令人兴奋的新进展不断出现。在这篇综述中，在全面总结了 Myc 驱动的癌症的潜在药物靶点的宝贵来源后，我们还展望了利用巨胞饮作用将 Omomyc 等肽或抗体制剂递送到细胞内隔室进行癌症治疗的光明前景。
The Myc proto-oncogene family consists of three members, C-MYC, MYCN, and MYCL, which encodes the transcription factor c-Myc (hereafter Myc), N-Myc, and L-Myc, respectively. Myc protein orchestrates diverse physiological processes, including cell proliferation, differentiation, survival, and apoptosis. Myc modulates about 15% of the global transcriptome, and its deregulation rewires the cellular signaling modules inside tumor cells, thereby acquiring selective advantages. The deregulation of Myc occurs in >70% of human cancers, and is related to poor prognosis; hence, hyperactivated Myc oncoprotein has been proposed as an ideal drug target for decades. Nevertheless, no specific drug is currently available to directly target Myc, mainly because of its “undruggable” properties: lack of enzymatic pocket for conventional small molecules to bind; inaccessibility for antibody due to the predominant nucleus localization of Myc. Although the topic of targeting Myc has actively been reviewed in the past decades, exciting new progresses in this field keep emerging. In this review, after a comprehensive summarization of valuable sources for potential druggable targets of Myc-driven cancer, we also peer into the promising future of utilizing macropinocytosis to deliver peptides like Omomyc or antibody agents to intracellular compartment for cancer treatment.
登录
查看更多内容
影响因子：
5.3
作者：
Farrell, Amy S.;Pelz, Carl;Sears, Rosalie C.
通讯作者：
Sears, Rosalie C.
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
11.5
作者：
Bucci, B;D'Agnano, I;Vecchione, A
通讯作者：
Vecchione, A
影响因子：
4.6
作者：
Castell A;Yan Q;Fawkner K;Hydbring P;Zhang F;Verschut V;Franco M;Zakaria SM;Bazzar W;Goodwin J;Zinzalla G;Larsson LG
通讯作者：
Larsson LG
影响因子：
3.4
作者：
Cercek, Andrea;Wheler, Jennifer;Saltz, Leonard
通讯作者：
Saltz, Leonard