In what is believed to be the most comprehensive molecular characterization to date of the most common type of head and neck cancer, researchers from the Johns Hopkins departments of pathology and oncology, the Johns Hopkins Kimmel Cancer Center, the Johns Hopkins University School of Medicine, and 18 other centers around the U.S. and Poland have clarified the contribution of key cancer-associated genes, proteins and signaling pathways in these cancers, while proposing possible new treatment avenues.
Their deep-dive investigation of HPV-negative head and neck squamous cell carcinomas (HNSCCs), described in the Jan. 7 issue of the journal Cancer Cell, involved tumors from 108 patients who had not yet received cancer treatment, and 66 samples of healthy tissue surrounding the tumors. The study systematically cataloged HPV-negative HNSCC-associated proteins, phosphosites (areas where they are modified by phosphate groups) and signaling pathways, finding three distinct subtypes of HNSCCs.
HNSCCs arise in the cells that line the upper aerodigestive tract, including the lips, mouth, tongue, nose, throat, vocal cords, and part of the esophagus and windpipe. The first subtype of HNSCC identified by researchers, dubbed CIN, showed the worst prognosis. It was associated with the larynx, a strong history of smoking and high instability of chromosomes. Because this subtype was associated with frequent aberrations of the CCND1 and CDKN2A genes, and high activity of the enzymes CDK4 and CDK6, this type of cancer may respond best to anti-cancer drugs called CDK4/6 inhibitors.
The second subtype, dubbed Basal, showed protein elevations of several basal factors, the most basic set of proteins needed to activate gene transcription. It was characterized by high activity in a signaling pathway called EGFR (epidermal growth factor receptor) and high expression of molecules called AREG and TNFA, which attach to the EGFR tumor protein.