Preferential targeting of cancer stem cells in the radiosensitizing effect of ABT-737 on HNSCC.
Head and neck squamous cell carcinomas (HNSCC) are common human malignancies with poor clinical outcomes. The 5-year survival rates for patients with advanced stage HNSCC have not changed appreciably in the past few decades, underscoring a dire need for improved therapeutic options. HNSCC is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome. The aim of this study was to evaluate combined effects of radiation and ABT-737, a BH3-mimetic molecule, in HNSCC. Although ABT-737, as a single agent, was largely ineffective at promoting HNSCC cell death, we found that combining ABT-737 and radiation induced strong synergistic apoptosis in HNSCC cell lines and delayed tumoral growth in vivo. Moreover, we demonstrated for the first time that ABT-737, alone or in combination with radiation, can efficiently eliminate cancer stem cells (CSCs). Altogether, our results indicate that therapy targeting anti-apoptotic Bcl-2 family members could be a highly effective potential adjuvant to radiotherapy capable of targeting CSCs in HNSCC and therefore overcoming cancer recurrence and metastasis.
['Gilormini|Marion|M|', 'Malesys|Céline|C|', 'Armandy|Emma|E|', 'Manas|Patrick|P|', 'Guy|Jean-Baptiste|JB|', 'Magné|Nicolas|N|', 'Rodriguez-Lafrasse|Claire|C|', 'Ardail|Dominique|D|']
D000818:Animals D017209:Apoptosis D001713:Biphenyl Compounds D002294:Carcinoma, Squamous Cell D045744:Cell Line, Tumor D006258:Head and Neck Neoplasms D006801:Humans D051379:Mice D016688:Mice, Inbred NOD D008819:Mice, Nude D016513:Mice, SCID D014411:Neoplastic Stem Cells D009596:Nitrophenols D010879:Piperazines D011838:Radiation-Sensitizing Agents D000077195:Squamous Cell Carcinoma of Head and Neck D013449:Sulfonamides D023041:Xenograft Model Antitumor Assays
cancer stem cells ABT-737 head and neck squamous cell carcinoma Bcl-2 family radiation