SMAD4 and head and neck squamous cell carcinoma: In this report, we address HNSCC and discuss future research opportunities using the Collaborative Cross (CC) mouse model and crossing it to mice carrying single or double knockout genes (e.g. Smad4 and P53 genes) to comprehensively identify genetic factors affecting the development of this complex by studying genome‐wide association study (GWAS), epigenetics, small and microRNA, long noncoding RNA (lncRNA), lncRNA, Histone modifications, Acetylation, Methylation, phosphorylation, and Proteomics.