动态 BH3 分析方法快速鉴定 BH3 模拟物耐药异种移植瘤小鼠模型中的有效治疗方法。

Dynamic BH3 profiling method for rapid identification of active therapy in BH3 mimetics resistant xenograft mouse models.

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute, 440 Brookline Avenue, M430, Boston, MA 02215, USA.

Harvard Medical School, 25 Shattuck Street, Boston, MA 02215, USA.

出版信息

STAR Protoc. 2021 May 12;2(2):100461. doi: 10.1016/j.xpro.2021.100461. eCollection 2021 Jun 18.

DOI:10.1016/j.xpro.2021.100461

PMID:34027474

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8131978/

Abstract

The clinical effectiveness of BH3 mimetics therapy is limited by the inevitable emergence of acquired resistance. We present a protocol to model acquired resistance to BH3 mimetics in patient-derived xenograft (PDX) mouse models of acute myeloid leukemia. Using resistant PDXs as a valuable model, we next introduce a protocol for dynamic BH3 profiling (DBP) method. DBP allows functional identification of effective drug therapies based on measurements of drug-induced apoptosis signaling to overcome BH3 mimetics resistance. For complete details on the use and execution of this protocol, please refer to Bhatt et al. (2020).

摘要

BH3 模拟物治疗的临床效果受到获得性耐药的必然出现的限制。我们提出了一个方案，以在急性髓系白血病的患者来源异种移植（PDX）小鼠模型中模拟获得性对 BH3 模拟物的耐药性。使用耐药性 PDX 作为有价值的模型，我们接下来引入了一种动态 BH3 分析（DBP）方法的方案。DBP 允许基于药物诱导的细胞凋亡信号的测量来对有效的药物治疗进行功能鉴定，以克服 BH3 模拟物的耐药性。有关该方案的使用和执行的完整详细信息，请参考 Bhatt 等人（2020 年）。