6月12日，Cancer Cell杂志报道了弥散性大B细胞淋巴瘤化学协同治疗的最新进展。
癌基因突变的知识，可催生靶向性杀死癌细胞而避免正常细胞受害的治疗手段。来那度胺在弥散性大B细胞淋巴瘤（DLBCL）的活化B细胞样（ABC）亚型中是一种活性药物。由于ABC DLBCL细胞中存在MYD88癌基因，来那度胺可通过促进干扰素β (IFNβ)的产生来杀死这些癌细胞。
来那度胺以cereblon依赖的方式下调IRF4和SPIB的水平。这两个转录因子一起通过抑制IRF7和上调促生存的NF-kappa-B信号通路预防IFNβ的产生。利用Bruton 的酚基乙氨酸激酶(BTK) 抑制剂ibrutinib阻断B细胞受体信号，也可下调IRF4，并与来那度胺协同杀伤ABC DLBCL细胞。该研究表明，ibrutinib与来那度胺结合或可成为新的治疗策略。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma
Yibin Yang, Arthur L. Shaffer, N.C. Tolga Emre, Michele Ceribelli, Meili Zhang, George Wright, Wenming Xiao, John Powell
Knowledge of oncogenic mutations can inspire therapeutic strategies that are synthetically lethal, affecting cancer cells while sparing normal cells. Lenalidomide is an active agent in the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), but its mechanism of action is unknown. Lenalidomide kills ABC DLBCL cells by augmenting interferon β (IFNβ) production, owing to the oncogenic MYD88 mutations in these lymphomas. In a cereblon-dependent fashion, lenalidomide downregulates IRF4 and SPIB, transcription factors that together prevent IFNβ production by repressing IRF7 and amplify prosurvival NF-B signaling by transactivating CARD11. Blockade of B cell receptor signaling using the BTK inhibitor ibrutinib also downregulates IRF4 and consequently synergizes with lenalidomide in killing ABC DLBCLs, suggesting attractive therapeutic strategies.
