Author/Authors :
Puyol، نويسنده , , Marta and Martيn، نويسنده , , Alberto and Dubus، نويسنده , , Pierre and Mulero، نويسنده , , Francisca and Pizcueta، نويسنده , , Pilar and Khan، نويسنده , , Gulfaraz and Guerra، نويسنده , , Carmen and Santamarيa، نويسنده , , David and Barbacid، نويسنده , , Mariano، نويسنده ,
Abstract :
Summary
e unveiled a synthetic lethal interaction between K-Ras oncogenes and Cdk4 in a 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 in lung cells that express an endogenous K-Ras oncogene. No such response occurs in lungs expressing a single Cdk4 allele or in other K-Ras-expressing tissues. More importantly, targeting Cdk4 alleles in advanced tumors detectable by computed tomography scanning also induces senescence and prevents tumor progression. These observations suggest that robust and selective pharmacological inhibition of Cdk4 may provide therapeutic benefit for NSCLC patients carrying K-RAS oncogenes.
