Together, these cooperating genetic alterations may represent additional therapeutic targets beyond MEK inhibition for NF1-associated high-grade gliomas, specifically using small molecule inhibitors of CDK4/6 (e.g., abemaciclib) and either PARP (e.g., olaparib) or ATR (e.g., berzosertib) given the known synthetic lethality in tumors that utilize alternative lengthening of telomeres [8, 10, 33]. This evidence concerns the gene CDK4 and glioma.