Format

Send to

Choose Destination
Cancer Cell. 2007 Aug;12(2):171-85.

BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Abstract

Cancer cells exhibit many abnormal phenotypes that induce apoptotic signaling via the intrinsic, or mitochondrial, pathway. That cancer cells nonetheless survive implies that they select for blocks in apoptosis. Identifying cancer-specific apoptotic blocks is necessary to rationally target them. Using a panel of 18 lymphoma cell lines, we show that a strategy we have developed, BH3 profiling, can identify apoptotic defects in cancer cells and separate them into three main classes based on position in the apoptotic pathway. BH3 profiling identifies cells that require BCL-2 for survival and predicts sensitivity to the BCL-2 antagonist ABT-737. BCL-2 dependence correlates with high levels of proapoptotic BIM sequestered by BCL-2. Strikingly, BH3 profiling can also predict sensitivity to conventional chemotherapeutic agents like etoposide, vincristine, and adriamycin.

PMID:
17692808
DOI:
10.1016/j.ccr.2007.07.001
[Indexed for MEDLINE]
Free full text

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center