A Synthetic Lethal Interaction between K-Ras Oncogenes and Cdk4 Unveils a Therapeutic Strategy for Non-small Cell Lung Carcinoma
作者： Marta Puyol , Alberto Martín , Pierre Dubus , Francisca Mulero , Pilar Pizcueta
DOI: 10.1016/J.CCR.2010.05.025
关键词:
摘要: We have unveiled a synthetic lethal interaction between K-Ras oncogenes and Cdk4 in mouse tumor model that closely recapitulates human non-small cell lung carcinoma (NSCLC). Ablation of Cdk4, but not Cdk2 or Cdk6, induces an immediate senescence response only cells express endogenous oncogene. No such occurs lungs expressing single allele other K-Ras-expressing tissues. More importantly, targeting alleles advanced tumors detectable by computed tomography scanning also prevents progression. These observations suggest robust selective pharmacological inhibition may provide therapeutic benefit for NSCLC patients carrying K-RAS oncogenes.
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