ArticlePloS one2011
Expression-based in silico screening of candidate therapeutic compounds for lung adenocarcinoma.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Prioritizing therapeutics for lung cancer: an integrative meta-analysis of cancer gene signatures and chemogenomic data.PLoS computational biology · 2015Pooled it
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- Cellular Stress-Modulating Drugs Can Potentially Be Identified by in Silico Screening with Connectivity Map (CMap).International journal of molecular sciences · 2019Review
- Systems Biology Approaches to Investigate Genetic and Epigenetic Molecular Progression Mechanisms for Identifying Gene Expression Signatures in Papillary Thyroid Cancer.International journal of molecular sciences · 2019Article
- Knockdown of B7H6 inhibits tumor progression in triple-negative breast cancer.Oncology letters · 2018Article
- A review of connectivity map and computational approaches in pharmacogenomics.Briefings in bioinformatics · 2018Review
- Long Non-Coding RNAs Serve as Diagnostic Biomarkers of Preeclampsia and Modulate Migration and Invasiveness of Trophoblast Cells.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
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- Drug discovery using clinical outcome-based Connectivity Mapping: application to ovarian cancer.BMC genomics · 2016Article
- Connectivity Map-based discovery of parbendazole reveals targetable human osteogenic pathway.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma.Oncotarget · 2015Article
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- Expression Profiling Identifies Bezafibrate as Potential Therapeutic Drug for Lung Adenocarcinoma.Journal of Cancer · 2015Article
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- A chemical genetic approach identifies piperazine antipsychotics as promoters of CNS neurite growth on inhibitory substrates.Molecular and cellular neurosciences · 2012Article
- Hsp90 inhibitors and drug resistance in cancer: the potential benefits of combination therapies of Hsp90 inhibitors and other anti-cancer drugs.Biochemical pharmacology · 2012Review
- Next-generation personalized drug discovery: the tripeptide GHK hits center stage in chronic obstructive pulmonary disease.Genome medicine · 2012Article
- Discovering biological connections between experimental conditions based on common patterns of differential gene expression.BMC bioinformatics · 2011Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLung adenocarcinom (AC) is the most common form of lung cancer. Currently, the number of medical options to deal with lung cancer is very limited. In this study, we aimed to investigate potential therapeutic compounds for lung adenocarcinoma based on integrative analysis. METHODOLOGY/PRINCIPAL
findingsThe candidate therapeutic compounds were identified in a two-step process. First, a meta-analysis of two published microarray data was conducted to obtain a list of 343 differentially expressed genes specific to lung AC. In the next step, expression profiles of these genes were used to query the Connectivity-Map (C-MAP) database to identify a list of compounds whose treatment reverse expression direction in various cancer cells. Several compounds in the categories of HSP90 inhibitor, HDAC inhibitor, PPAR agonist, PI3K inhibitor, passed our screening to be the leading candidates. On top of the list, three HSP90 inhibitors, i.e. 17-AAG (also known as tanespimycin), monorden, and alvespimycin, showed significant negative enrichment scores. Cytotoxicity as well as effects on cell cycle regulation and apoptosis were evaluated experimentally in lung adenocarcinoma cell line (A549 or GLC-82) with or without treatment with 17-AAG. In vitro study demonstrated that 17-AAG alone or in combination with cisplatin (DDP) can significantly inhibit lung adenocarcinoma cell growth by inducing cell cycle arrest and apoptosis. CONCLUSIONS/SIGNIFICANCE: We have used an in silico screening to identify compounds for treating lung cancer. One such compound 17-AAG demonstrated its anti-lung AC activity by inhibiting cell growth and promoting apoptosis and cell cycle arrest.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.