A Kinome-Wide Synthetic Lethal CRISPR/Cas9 Screen Reveals That mTOR Inhibition Prevents Adaptive Resistance to CDK4/CDK6 Blockade in HNSCC.
Yusuke GotoKeiichi KoshizukaToshinori AndoHiroki IzumiXingyu WuKuniaki SatoTomohiko IshikawaKyle FordXiaodong FengZhiyong WangNadia ArangMichael M AllevatoAyush KishorePrashant MaliJorge Silvio GutkindPublished in: Cancer research communications (2024)
A kinome-wide CRISPR/Cas9 screen identified cell-cycle inhibition as a synthetic lethal target of mTORis. A combination of mTORi and palbociclib, a CDK4/6-specific inhibitor, showed strong synergistic effects in HNSCC. Mechanistically, mTORis inhibited palbociclib-induced increase in CCNE1.