title: Radioresistance in head and neck squamous cell carcinoma: Biological bases and therapeutic implications.
abstract: Head and neck squamous cell carcinoma (HNSCC) is strongly associated with alcohol and tobacco consumption. Lately, the incidence of human papillomavirus (HPV)-related tumors has shown a significant increase, and HPV-related tumors show distinctive features if compared with the HPV-negative counterpart. Locally advanced HNSCC can be treated with concomitant chemoradiotherapy, but early recurrences sometimes occur. Relapses are often related to an intrinsic radioresistance of the tumors. Alterations in intracellular pathways, primarily involved in cell proliferation, apoptosis, and DNA repair, can lead to radioresistance. Preclinical and clinical evidence highlighted that 3 main pathways, including the epidermal growth factor receptor (EGFR), the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and the p53 signaling cascades, play a crucial role in radioresistance development. A future approach may consist in the association of radiotherapy (RT) and selective inhibition of the key pathways involved in radioresistance. Phase I, II, and III clinical trials are currently testing these novel treatment strategies.
authors.affiliation: Head and Neck Medical Oncology Unit, National Tumor Institute of Naples, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perri
authors.forename: Roberto
authors.initials: R
authors.lastname: Pacelli
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Della Vittoria Scarpati
authors.forename: Laura
authors.initials: L
authors.lastname: Cella
authors.forename: Mario
authors.initials: M
authors.lastname: Giuliano
authors.forename: Francesco
authors.initials: F
authors.lastname: Caponigro
authors.forename: Stefano
authors.initials: S
authors.lastname: Pepe
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy / Q000379:methods*; D066246:ErbB Receptors / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D011379:Prognosis; D011836:Radiation Tolerance / Q000502:physiology / Q000528:radiation effects*; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects / Q000528:radiation effects; D016896:Treatment Outcome
chemical_list: C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D058570:TOR Serine-Threonine Kinases
keywords: Akt; P53; chemoradiotherapy; epidermal growth factor receptor (EGFR); head and neck squamous cell carcinoma; intracellular pathway; radioresistance