Expression data from tumor lungs after continuous vs. pulsatile selumetinib treatment in KRASG12C GEMM

KRAS is one of the driver oncogenes in non-small cell lung cancer (NSCLC), but remains refractory to current modalities of targeted pathway inhibition, which include inhibiting downstream kinase MEK to circumvent KRAS activation. Here, we show that pulsatile, rather than continuous, treatment with MEK inhibitors (MEKis) maintains T cell activation and better control tumor growth and survival. We used microarrays to examine the MAPK signaling pathway suppression from tumor lungs of KRASG12C GEMM after continuous vs. pulsatile treatment of selumetinib. Tumor was induced by intranasal administration of adenoviral-Cre to KRASLSL-G12C/+ GEMM mice. Once the tumor size reached approximately 500 mm3 (at about 12 weeks after adenoviral inoculation), KRASG12C GEMM mice were treated with selumetinib continuously (daily for 3 weeks, 25mg/kg, BID) or pulsatilely (1 cycle: 1 week ON + 1 week OFF, total 3 cycles, 25mg/kg, BID) with their matched control (vehicles), since the treatments were not done at the same time. The mice were sacrificed after selumetinib treatment is completed.