Human Gene Set: MARCHINI_TRABECTEDIN_RESISTANCE_DN


Standard name MARCHINI_TRABECTEDIN_RESISTANCE_DN
Systematic name M8349
Brief description Genes down-regulated in chondrosarcoma and ovarian carcinoma cell lines which developed resistance to trabectedin [PubChem=3199].
Full description or abstract ET-743 (Yondelis(TM), Trabectedin) isolated from the tunicate Ecteinascidia turbinata, is being tested in phase II clinical trials in Europe and the United States of America (USA). Studies with different solid tumours have shown antitumour activity in advanced, pre-treated sarcomas as well as in drug-resistant breast and ovarian cancer. The primary mechanism of action for ET-743 has not been fully elucidated and different models have been suggested to explain its molecular mechanism of action. ET-743 binds tightly to the minor groove of DNA and previous data have suggested that ET-743 acts by interfering with RNA transcription. To further investigate the mechanism of in vitro drug resistance, we evaluated the gene expression profile in ovarian and chondrosarcoma cell lines selected for resistance to ET-743. We found 70 genes whose expression was modulated in both drug-resistant cell lines when compared with their respective parental drug-sensitive cell lines. This pattern of gene expression seems to be selective for ET-743-resistant cells, since ovarian cancer cells resistant to paclitaxel did not share the same gene expression changes. Data presented in this study reveal different molecular pathways that could be involved in the cellular mechanism of ET-743 resistance.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15661559   Authors: Marchini S,Marrazzo E,Bonomi R,Chiorino G,Zaffaroni M,Weissbach L,Hornicek FJ,Broggini M,Faircloth GT,D'Incalci M
Exact source Suppl. file: CHS & Igrovs with common trend: down
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Source species Homo sapiens
Contributed by John Newman (University of Washington)
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HUMAN_SEQ_ACCESSION
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Version history 3.0: Renamed from ET743_RESIST_DN

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