YL064 activates proteasomal-dependent degradation of c-Myc and synergistically enhances the anti-tumor activity of ABT-199 in diffuse large B cell lymphoma
YL064 activates proteasomal-dependent degradation of c-Myc and synergistically enhances the anti-tumor activity of ABT-199 in diffuse large B cell lymphoma
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DOI：
10.1038/s41392-020-00236-1
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发表时间：
2020
影响因子：
39.3
通讯作者：
Wu Yingli
中科院分区：
文献类型：
--
作者：
Shan Huizhuang;Cao Yang;Xiao Xinhua;Liu Meng;Wu Yunzhao;Zhu Qi;Xu Hanzhang;Lei Hu;Yao Zhujun;Wu Yingli
c-Myc is highly associated with poor prognosis and aggressive progression of diffuse large B cell lymphoma (DLBCL) and is thus a desirable drug target. Moreover, studies indicate that 5-15% of DLBCL patients harbor MYC and BCL-2 translocations, while 20-35% DLBCL patients simultaneously overexpress of c-Myc and BCL-2 proteins without gene rearrangements. These two types of DLBCL are referred as "double-hit" lymphoma (DHL) and "double-expressor" lymphoma (DEL), respectively. Both DHL and DEL lymphomas have inferior clinical outcomes and are refractory to R-CHOP or even hematopoietic stem cell transplant.2 Thus, targeting both c-Myc and BCL-2 is a promising strategy to treat high-risk DLBCLs. Although BCL-2 inhibitors are clinically available, c-Myc remains to be "undruggable" owing to its lack of kinase activity and intrinsically disordered structure. Thus, developing clinically applicable c-Myc inhibitor remains challenging.
