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Cell. 2015 Feb 26;160(5):977-989. doi: 10.1016/j.cell.2015.01.042.

Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy.

Author information

1
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
2
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
3
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
4
Hematology/Oncology Department of Medicine, Massachusetts General Hospital, Boston, MA 02114,USA.
5
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: anthony_letai@dfci.harvard.edu.

Abstract

There is a lack of effective predictive biomarkers to precisely assign optimal therapy to cancer patients. While most efforts are directed at inferring drug response phenotype based on genotype, there is very focused and useful phenotypic information to be gained from directly perturbing the patient's living cancer cell with the drug(s) in question. To satisfy this unmet need, we developed the Dynamic BH3 Profiling technique to measure early changes in net pro-apoptotic signaling at the mitochondrion ("priming") induced by chemotherapeutic agents in cancer cells, not requiring prolonged ex vivo culture. We find in cell line and clinical experiments that early drug-induced death signaling measured by Dynamic BH3 Profiling predicts chemotherapy response across many cancer types and many agents, including combinations of chemotherapies. We propose that Dynamic BH3 Profiling can be used as a broadly applicable predictive biomarker to predict cytotoxic response of cancers to chemotherapeutics in vivo.

PMID:
25723171
PMCID:
PMC4391197
DOI:
10.1016/j.cell.2015.01.042
[Indexed for MEDLINE]
Free PMC Article

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