用分子匹配疗法的瘤突变负担和生存率
Till de Bortoli1, Manuela Benary2, Peter Horak3
1Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.
概括
高瘤突变负担 (TMB) 预测了接受分子匹配癌症治疗的患者的不良结果,这表明了耐药性途径. TMB值得进一步研究,因为它是精确瘤学的预测生物标志物.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 精准医学是一门精准的医学.
背景情况:
- 对于分子匹配的癌症疗法,瘤突变负担 (TMB) 的预测价值仍然不清楚.
- 由于同时发生的驱动突变,高的TMB可能表明对向治疗的耐药性.
研究的目的:
- 为了研究TMB对分子匹配疗法治疗患者后果的影响.
- 探索TMB,同时发生的突变和晚期癌症治疗反应之间的关系.
主要方法:
- 对患有晚期癌症的患者进行了分子分析和TMB分析.
- 在发现和验证队列中,高TMB和低TMB组之间的生存结果 (总生存和无进展生存) 进行了比较.
- 使用患者数据和癌症基因组图谱 (TCGA) 数据集评估了同时发生的驱动突变和TMB之间的相关性.
主要成果:
- 与低TMB患者相比,接受分子匹配治疗的高TMB患者的整体存活时间和无进展存活时间显著较短.
- 这些发现在一个独立的队列中得到了验证,证实了高TMB和针对性治疗的不良结果之间的关联.
- 在接受非分子告知疗法治疗的患者中,无论TMB水平如何,都没有观察到生存率的显著差异.
- 在多个数据集中,同时发生的驱动器突变和TMB之间发现了强烈的相关性.
结论:
- 高TMB与接受分子匹配治疗的患者的不良结果有关,这表明存在抗药机制.
- 瘤突变负担应进一步评估,作为精确瘤学倡议中的预测生物标志物.
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