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Transcription profiling of human naive SCLC cell lines

ABSTRACT: RNA expression analysis was performed to compare patterns to DNA copy number changes and sensitivity to BCL2 inhibitors. Experiment Overall Design: Naive cell lines were isolated in duplicate or triplicate (only a single for H69AR) to determine RNA expression pattern.

ORGANISM(S): Homo sapiens

SUBMITTER: Mark Anderson

PROVIDER: E-GEOD-7097 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Integrative genomic analysis of small-cell lung carcinoma reveals correlates of sensitivity to bcl-2 antagonists and uncovers novel chromosomal gains.

Olejniczak Edward T ET Van Sant Charles C Anderson Mark G MG Wang Gang G Tahir Stephen K SK Sauter Guido G Lesniewski Rick R Semizarov Dimitri D

Molecular cancer research : MCR 20070401 4

Cancer is a highly heterogeneous disease in terms of the genetic profile and the response to therapeutics. An early identification of a genomic marker in drug discovery may help select patients that would respond to treatment in clinical trials. Here we suggest coupling compound screening with comparative genomic hybridization analysis of the model systems for early discovery of genomic biomarkers. A Bcl-2 antagonist, ABT-737, has recently been discovered and shown to induce regression of solid ...[more]

PMID: 17426248

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SCLC cell line profiling on HG-U133A arrays

Project description:RNA expression analysis was performed to compare patterns to DNA copy number changes and sensitivity to BCL2 inhibitors. Keywords: cell line comparison

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Transcription profiling of human SCLC cell line set 2

Project description: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 (KiÃ¢??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. Experiment Overall Design: Naive cell lines were isolated in duplicate or triplicate (only a single for H69AR) to determine RNA expression pattern.

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