CDK4 and melanoma: For patients with NRAS mutant melanomas, there have been several clinical trials of combination therapy: combination of CDK4/6 inhibitor (LEE011) and MEK inhibitor (MEK162) in phase Ib/II clinical trial [40], and combination of RAF inhibitor (LXH254) with ERK1/2 inhibitor (LTT462) or Trametinib (MEK inhibitor) in phase Ib clinical trial [41].