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- W4362479079 abstract "<div>Abstract<p>The MEK1 and MEK2 inhibitor GSK1120212 is currently in phase II/III clinical development. To identify predictive biomarkers, sensitivity to GSK1120212 was profiled for 218 solid tumor cell lines and 81 hematologic malignancy cell lines. For solid tumors, <i>RAF</i>/<i>RAS</i> mutation was a strong predictor of sensitivity. Among <i>RAF/RAS</i> mutant lines, co-occurring <i>PIK3CA</i>/<i>PTEN</i> mutations conferred a cytostatic response instead of a cytotoxic response for colon cancer cells that have the biggest representation of the comutations. Among <i>KRAS</i> mutant cell lines, transcriptomics analysis showed that cell lines with an expression pattern suggestive of epithelial-to-mesenchymal transition were less sensitive to GSK1120212. In addition, a proportion of cell lines from certain tissue types not known to carry frequent <i>RAF</i>/<i>RAS</i> mutations also seemed to be sensitive to GSK1120212. Among these were breast cancer cell lines, with triple negative breast cancer cell lines being more sensitive than cell lines from other breast cancer subtypes. We identified a single gene <i>DUSP6</i>, whose expression was associated with sensitivity to GSK1120212 and lack of expression associated with resistance irrelevant of <i>RAF/RAS</i> status. Among hematologic cell lines, acute myeloid leukemia and chronic myeloid leukemia cell lines were particularly sensitive. Overall, this comprehensive predictive biomarker analysis identified additional efficacy biomarkers for GSK1120212 in <i>RAF/RAS</i> mutant solid tumors and expanded the indication for GSK1120212 to patients who could benefit from this therapy despite the <i>RAF/RAS</i> wild-type status of their tumors. <i>Mol Cancer Ther; 11(3); 720–9. ©2011 AACR</i>.</p></div>" @default.
- W4362479079 created "2023-04-05" @default.
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- W4362479079 date "2023-04-03" @default.
- W4362479079 modified "2023-09-26" @default.
- W4362479079 title "Data from Comprehensive Predictive Biomarker Analysis for MEK Inhibitor GSK1120212" @default.
- W4362479079 doi "https://doi.org/10.1158/1535-7163.c.6535302.v1" @default.
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