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Series GSE10841 Query DataSets for GSE10841
Status Public on May 01, 2008
Title SCLC cell line profiling on HG-U133A arrays set 2
Organism Homo sapiens
Experiment type Expression profiling by array
Summary RNA expression analysis was performed to compare patterns to sensitivity to BCL2 inhibitors (ABT-263).
Overexpression of the prosurvival Bcl-2 family members (Bcl-2, Bcl-xL and Mcl-1) is commonly associated with tumor maintenance, progression and chemoresistance. We previously reported the discovery of ABT-737, a potent, small molecule Bcl-2 family protein inhibitor. A major limitation of ABT-737 is that it is not orally bioavailable. This may limit its use for chronic single agent treatment and the flexibility to dose in combination with parenteral chemotherapy. Here we report the discovery and biological properties of ABT-263, a potent, orally bioavailable Bad-like BH3 mimetic (KiĆ¢??s of < 1 nM for Bcl-2, Bcl-xL and Bcl-w). The oral bioavailability of ABT-263 in preclinical animal models is 20% - 50%, depending on formulation. ABT-263 disrupts Bcl-2/Bcl-xL interactions with pro-death proteins (e.g., Bim) in cells leading to the initiation of apoptosis within 2 hr post-treatment. In human tumor cells, ABT-263 rapidly induces Bax translocation, cytochrome c release and subsequent programmed cell death. Oral administration of ABT-263 alone induces complete tumor regressions in xenograft models of small cell lung cancer and acute lymphoblastic leukemia. In xenograft models of aggressive B-cell lymphoma and multiple myeloma where ABT-263 exhibits modest or no single agent activity, it significantly enhances the efficacy of clinically relevant therapeutic regimens. These data provide the rationale for clinical trials evaluating ABT-263 in SCLC and B-cell malignancies. The oral efficacy of ABT-263 should provide dosing flexibility to maximize clinical utility as both a single agent and in combination with standard chemotherapeutic regimens.
Keywords: cell line comparison
Overall design Naive cell lines were isolated in duplicate or triplicate (only a single for H69AR) to determine RNA expression pattern.
Contributor(s) Anderson MG, Tahir SK
Citation(s) 18451170
Submission date Mar 14, 2008
Last update date Dec 06, 2018
Contact name Mark Anderson
Organization name Abbott Laboratories
Department GPRD/R4CT
Lab AP10-2
Street address 100 Abbott Park Road
City Abbott Park
State/province IL
ZIP/Postal code 60064
Country USA
Platforms (1)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (46)
GSM170706 NCI-H211 cell line (NCI-H211a)
GSM170707 NCI-H211 cell line (NCI-H211c)
GSM170708 NCI-H510 cell line (NCI-H510a)
BioProject PRJNA107325

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE10841_RAW.tar 87.6 Mb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table

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