【佳学基因检测】抑制 ERK 二聚化可改善 BRAF 驱动的甲状腺未分化癌

品牌基因检测怎么样排队

分析明白《Cell Mol Life Sci》在. 2022 Sep 3;79(9):504.发表了一篇题目为《抑制 ERK 二聚化可改善 BRAF 驱动的甲状腺未分化癌》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Miguel A Zaballos #, Adrián Acuña-Ruiz #, Marta Morante, Garcilaso Riesco-Eizaguirre, Piero Crespo, Pilar Santisteban等完成。促进了肿瘤的正确治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及正确治疗临床研究内容关键词：

布拉夫,德尔-22379, ERK 二聚化, RAS,甲状腺癌

肿瘤靶向治疗基因检测临床应用结果

背景：RAS-to-ERK 信号传导对晚期甲状腺癌的发病和进展至关重要，阻断 ERK 二聚化可在几种人类癌症中提供治疗益处。在这里，我们分析了 DEL-22379（一种相对特异性的 ERK 二聚化抑制剂）对 RAS-to-ERK 信号级联的激活以及体外和体内肿瘤相关过程的影响。方法：我们使用了一组四人具有 BRAF 或 RAS 突变的间变性甲状腺癌 (ATC) 细胞系以分析 ERK 动力学和肿瘤特异性特征。我们还使用 RNA 测序评估了 DEL-22379 对 ATC 细胞系转录景观的影响，并评估了其在 ATC 原位小鼠模型中的治疗效果。结果：DEL-22379 损害了 BRAF 中的上游 ERK 活化，但不损害 RAS-突变细胞。 DEL-22379 治疗减弱了细胞活力和转移相关过程，但主要在 BRAF 突变细胞中，而 BRAF 突变细胞的体内肿瘤生长和传播显着降低，而 RAS 突变细胞则轻度降低。转录组学分析表明，DEL-22379 以相反的方向调节 BRAF 和 RAS 突变细胞的转录景观。结论：我们的研究结果表明，BRAF 和 RAS 突变的甲状腺细胞对 DEL-22379 的反应不同，这不能用先前描述的抑制剂的作用机制。尽管如此，DEL-22379 在体内表现出对 BRAF 突变细胞的显着抗肿瘤作用，且明显缺乏毒性，使其成为开发组合治疗的有趣候选者。我们的数据强调了甲状腺癌发病和进展的特定驱动突变引起的差异，在实验和临床方法中应考虑这一点。德尔-22379； ERK 二聚化； RAS；甲状腺癌。

肿瘤发生与反复转移国际数据库描述：

Background: RAS-to-ERK signaling is crucial for the onset and progression of advanced thyroid carcinoma, and blocking ERK dimerization provides a therapeutic benefit in several human carcinomas. Here we analyzed the effects of DEL-22379, a relatively specific ERK dimerization inhibitor, on the activation of the RAS-to-ERK signaling cascade and on tumor-related processes in vitro and in vivo.Methods: We used a panel of four human anaplastic thyroid carcinoma (ATC) cell lines harboring BRAF or RAS mutations to analyze ERK dynamics and tumor-specific characteristics. We also assessed the impact of DEL-22379 on the transcriptional landscape of ATC cell lines using RNA-sequencing and evaluated its therapeutic efficacy in an orthotopic mouse model of ATC.Results: DEL-22379 impaired upstream ERK activation in BRAF- but not RAS-mutant cells. Cell viability and metastasis-related processes were attenuated by DEL-22379 treatment, but mostly in BRAF-mutant cells, whereas in vivo tumor growth and dissemination were strongly reduced for BRAF-mutant cells and mildly reduced for RAS-mutant cells. Transcriptomics analyses indicated that DEL-22379 modulated the transcriptional landscape of BRAF- and RAS-mutant cells in opposite directions.Conclusions: Our findings establish that BRAF- and RAS-mutant thyroid cells respond differentially to DEL-22379, which cannot be explained by the previously described mechanism of action of the inhibitor. Nonetheless, DEL-22379 demonstrated significant anti-tumor effects against BRAF-mutant cells in vivo with an apparent lack of toxicity, making it an interesting candidate for the development of combinatorial treatments. Our data underscore the differences elicited by the specific driver mutation for thyroid cancer onset and progression, which should be considered for experimental and clinical approaches.Keywords: BRAF; DEL-22379; ERK dimerization; RAS; Thyroid cancer.