title: The STAT3 pathway as a therapeutic target in head and neck cancer: Barriers and innovations.
abstract: Proteins of the signal transducer and activator of transcription (STAT) family mediate cellular responses to cytokines and growth factors. Aberrant regulation of the STAT3 oncogene contributes to tumor formation and progression in many cancers, including head and neck squamous cell carcinoma (HNSCC), where hyperactivation of STAT3 is implicated in both treatment resistance and immune escape. There are no oncogenic gain-of-function mutations in HNSCC. Rather, aberrant STAT3 signaling is primarily driven by upstream growth factor receptors, such as Janus kinase (JAK) and epidermal growth factor receptor (EGFR). Moreover, genomic silencing of select protein tyrosine phosphatase receptors (PTPRs), tumor suppressors that dephosphorylate STAT3, may lead to prolonged phosphorylation and activation of STAT3. This review will summarize current knowledge of the STAT3 pathway and its contribution to HNSCC growth, survival, and resistance to standard therapies, and discuss STAT3-targeting agents in various phases of clinical development.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Geiger
authors.affiliation: Department of Otolaryngology, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States. Electronic address: baumanje@upmc.edu.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Bauman
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D019281:Dimerization; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor
keywords: Head and neck cancer; STAT3