CDK4 and neoplasm: Multiple therapeutic synergies pairing anti-PD/PD-L1 agents with chemotherapy, radiation therapy, molecular targeted therapies like HER-2 targeted agents and inhibitors of VEGF, CDK4/6, PARP, HDAC, BRAF, MEK, and other checkpoint inhibitors like TIM-3 and LAG-3 (NCT04370704) have been considered in order to overcome the well-characterized challenges of tumor immune escape mechanisms (95, 233–236).