RESUMO
Radiation therapy plays an essential role in the treatment of head and neck squamous cell carcinoma (HNSCC), yet therapeutic efficacy is hindered by treatment-associated toxicity and tumor recurrence. In comparison to other cancers, innovation has proved challenging, with the epidermal growth factor receptor (EGFR) antibody cetuximab being the only new radiosensitizing agent approved by the FDA in over half a century. This review examines the physiological mechanisms that contribute to radioresistance in HNSCC as well as preclinical and clinical data regarding novel radiosensitizing agents, with an emphasis on those with highest translational promise.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Cetuximab/farmacologia , Neoplasias de Cabeça e Pescoço/radioterapia , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Dano ao DNA , Humanos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
We examined the antineoplastic effects of the iron chelators, deferasirox and deferoxamine in multiple myeloma cell lines as well as primary myeloma cells. These iron chelators showed marked antiproliferative activity as well as cytotoxicity toward myeloma cell lines and deferasirox was cytotoxic to bone marrow plasma cells from myeloma patients. We also demonstrate that autophagy induced by iron deprivation is the dominant mechanism that mediates the cytotoxicity of iron chelators in multiple myeloma. Exposure to iron chelators led to repression of mTOR signaling as evidenced by decreased phosphorylation of its target p70S6 kinase. Iron chelation, in particular with deferasirox has the potential to be readily translated to a clinical trial for multiple myeloma.
