Dual PI3K/mTOR Inhibitor NVP-BEZ235 Leads to a Synergistic Enhancement of Cisplatin and Radiation in Both HPV-Negative and -Positive HNSCC Cell Lines

Head and neck cancers (HNSCCs), especially in the advanced stages, are predominantly treated by radiochemotherapy, including cisplatin. The cure rates are clearly higher for HPV-positive HNSCCs when compared to HPV-negative HNSCCs. For both entities, this treatment is accompanied by serious adverse...

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Autoren: Subtil, Florentine S. B., Gröbner, Carolin, Recknagel, Niklas, Parplys, Ann Christin, Kohl, Sibylla, Arenz, Andrea, Eberle, Fabian, Dikomey, Ekkehard, Engenhart-Cabillic, Rita, Schötz, Ulrike
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Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2023
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Zusammenfassung:Head and neck cancers (HNSCCs), especially in the advanced stages, are predominantly treated by radiochemotherapy, including cisplatin. The cure rates are clearly higher for HPV-positive HNSCCs when compared to HPV-negative HNSCCs. For both entities, this treatment is accompanied by serious adverse reactions, mainly due to cisplatin administration. We reported earlier that for both HPV-positive and negative HNSCC cells, the effect of radiotherapy was strongly enhanced when pretreated using the dual PI3K/mTOR inhibitor NVP-BEZ235 (BEZ235). The current study shows that for HPV-positive cells, BEZ235 will strongly enhance the effect of cisplatin alone. More important, preincubation with BEZ235 was found to alter the purely additive effect normally seen when cisplatin is combined with radiation into a strong synergistic enhancement. This tri-modal combination might allow for the enhancement of the effect of radiochemotherapy, even with reduced cisplatin.
Beschreibung:Gefördert durch den Open-Access-Publikationsfonds der UB Marburg.
Umfang:16 Seiten
DOI:10.3390/cancers14133160