Combining radiation to EGFR and Bcl-2 blockade: a new approach to target cancer stem cells in head and neck squamous cell carcinoma
| Autor: | Nicolas Vial, Sophie Espenel, Claire Rodriguez-Lafrasse, Anne-Sophie Wozny, Dominique Ardail, Nicolas Magné, M.-A. Garcia, Safa Louati, Arnaud Gauthier, Gersende Alphonse, Jean-Baptiste Guy, Céline Malésys |
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| Přispěvatelé: | Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL) |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Cell [SDV.CAN]Life Sciences [q-bio]/Cancer 03 medical and health sciences 0302 clinical medicine Nude mouse Cancer stem cell Medicine EGFR inhibitors biology Cetuximab business.industry Cell growth General Medicine biology.organism_classification medicine.disease Head and neck squamous-cell carcinoma 3. Good health 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Stem cell business medicine.drug |
| Zdroj: | Journal of Cancer Research and Clinical Oncology Journal of Cancer Research and Clinical Oncology, Springer Verlag, 2021, 147 (7), pp.1905-1916. ⟨10.1007/s00432-021-03593-8⟩ |
| ISSN: | 1432-1335 0171-5216 |
| DOI: | 10.1007/s00432-021-03593-8 |
| Popis: | International audience; PurposeThe clinical outcome of head and neck squamous cell carcinoma (HNSCC) remains poor, partly due to the presence of resistant cancer stem cells (CSCs) which are responsible of recurrences. CSCs have low EGFR expression and, conversely, overexpress the anti-apoptotic Bcl-2 protein, which is involved in resistance to apoptosis and the invasion/migration capacities of tumour cells.MethodsThe combination therapy of ABT-199, a Bcl-2 inhibitor, cetuximab an EGFR inhibitor, and radiation using an HNSCC model (SQ20B cell line) and its corresponding CSC subpopulation were evaluated in vitro (2D/3D cell proliferation; invasion/migration and apoptosis using videomicroscopy) and in vivo.ResultsCetuximab strongly inhibited 2D and 3D cell proliferation, as well as invasion/migration, only in non-CSC-SQ20B cells, whereas ABT-199 selectively inhibited these mechanisms in SQ20B/CSCs. The combination of irradiation + cetuximab + ABT-199 increased the inhibition of the 2D and 3D cell proliferation, invasion/migration, and resistance to apoptosis in both cell sub-populations. In addition, in a nude mouse model with heterotopic tumour xenograft, a treatment combining cetuximab + ABT-199 with fractional irradiation strongly delayed the tumour growth and increased in vivo lifespan without side effects.ConclusionBased on the present results, this triple combination therapy may represent a new opportunity for testing in clinical trials, particularly in locally advanced HNSCC |
| Databáze: | OpenAIRE |
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