CDK4 and cancer: As KRAS and BRAF mutations are identified as the drug-resistant mutations of cetuximab, Yao et al. established a PDX trial and validated that concurrent inhibition of RAS and EGFR had a synergistic effect on the treatment of BRAF and KRAS mutation cancer models.48 Zhao et al. established the HER2 + PDX model and confirmed the efficacy of neratinib, a pan-HER tyrosine kinase inhibitor, in combination with CDK4/6, mTOR, or MEK inhibitors in the context of HER2 + cancer.189 DNA-dependent protein kinase (DNA-PK) plays essential roles in DNA damage response and repair.