Radioresistance in head and neck squamous cell carcinoma: Biological bases and therapeutic implications

Francesco Perri, Roberto Pacelli, Giuseppina Della Vittoria Scarpati, Laura Cella, Mario Giuliano, Francesco Caponigro, Stefano Pepe

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)763-770
Number of pages8
JournalHead and Neck
Issue number5
Publication statusPublished - May 1 2015


  • Akt
  • chemoradiotherapy
  • epidermal growth factor receptor (EGFR)
  • head and neck squamous cell carcinoma
  • intracellular pathway
  • P53
  • radioresistance

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Medicine(all)


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