Towards system genetics analysis of head and neck squamous cell carcinoma using the mouse model, cellular platform, and clinical human data

Head and neck squamous cell cancer (HNSCC) is a leading global malignancy. Every year, More than 830 000 people are diagnosed with HNSCC globally, with more than 430 000 fatalities. HNSCC is a deadly diverse malignancy with many tumor locations and biological characteristics. It originates from the squamous epithelium of the oral cavity, oropharynx, nasopharynx, larynx, and hypopharynx. The most frequently impacted regions are the tongue and larynx. Previous investigations have demonstrated the critical role of host genetic susceptibility in the progression of HNSCC. Despite the advances in our knowledge, the improved survival rate of HNSCC patients over the last 40 years has been limited. Failure to identify the molecular origins of development of HNSCC and the genetic basis of the disease and its biological heterogeneity impedes the development of new therapeutic methods. These results indicate a need to identify more genetic factors underlying this complex disease, which can be better used in early detection and prevention strategies. The lack of reliable animal models to investigate the underlying molecular processes is one of the most significant barriers to understanding HNSCC tumors. In this report, we explore and discuss potential research prospects utilizing the Collaborative Cross mouse model and crossing it to mice carrying single or double knockout genes (e.g. Smad4 and P53 genes) to identify genetic factors affecting the development of this complex disease using genome-wide association studies, epigenetics, microRNA, long noncoding RNA, lncRNA, histone modifications, methylation, phosphorylation, and proteomics.