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Radioresistance in head and neck squamous cell carcinoma: Biological bases and therapeutic implications
Author(s) -
Perri Francesco,
Pacelli Roberto,
Della Vittoria Scarpati Giuseppina,
Cella Laura,
Giuliano Mario,
Caponigro Francesco,
Pepe Stefano
Publication year - 2015
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.23837
Subject(s) - radioresistance , head and neck squamous cell carcinoma , cancer research , pi3k/akt/mtor pathway , epidermal growth factor receptor , medicine , oncology , protein kinase b , radiation therapy , chemoradiotherapy , head and neck cancer , biology , apoptosis , cancer , biochemistry
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. © 2015 Wiley Periodicals, Inc. Head Neck 37: 763–770, 2015