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

  • STAR Protoc. 2021 May 12;2(2):100461. doi: 10.1016/j.xpro.2021.100461.
Elyse A Olesinski  1  2 ,  Shruti Bhatt  1  2  3
Affiliations
  • 1. Department of Medical Oncology, Dana-Farber Cancer Institute, 440 Brookline Avenue, M430, Boston, MA 02215, USA.
  • 2. Harvard Medical School, 25 Shattuck Street, Boston, MA 02215, USA.
  • 3. Department of Pharmacy, National University of Singapore, 21 Lower Kent Ridge Road, Singapore 119077, Singapore.
PMID: 34027474 DOI: 10.1016/j.xpro.2021.100461
Abstract

The clinical effectiveness of BH3 mimetics therapy is limited by the inevitable emergence of acquired resistance. We present a protocol to model in vivo 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 in vivo BH3 mimetics resistance. For complete details on the use and execution of this protocol, please refer to Bhatt et al. (2020).

Keywords
Cancer; Cell isolation; Flow Cytometry/Mass Cytometry; Model Organisms.
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