Abstract
Radiotherapy has a central role in the treatment of head and neck squamous cell carcinoma (HNSCC). Activation of the PI3K/AKT/mTOR pathway can decrease the efficiency of radiotherapy via the promotion of cell survival and DNA repair. Here, the influence of PI3K pathway inhibition on radiotherapy response was investigated. Two PI3K inhibitors were investigated and both BKM120 and GDC0980 effectively inhibited cellular and clonogenic growth in 6 HNSCC cells, both HPV-positive as well as HPV-negative. Despite targeted inhibition of the pathway and slight increase in DNA damage, PI3K inhibition did not show significant radiosensitization. Currently only one clinical trial is assessing the effectiveness of combining BKM120 with RT in HNSCC (NCT02113878) of which the results are eagerly awaited.
Highlights
Radiotherapy has a central role in the treatment of head and neck squamous cell carcinoma (HNSCC)
In this study we investigated the response to a pan phosphatidylinositol 3 kinase (PI3K) inhibitor, BKM120, and a dual PI3K/mTOR inhibitor, GDC0980, in three human papillomavirus (HPV)-positive and three HPV-negative HNSCC cell lines alone and in combination with RT
We investigated the radiosensitizing potential of PI3K/AKT/mTOR pathway inhibitors in a panel of six HNSCC cell lines
Summary
Radiotherapy has a central role in the treatment of head and neck squamous cell carcinoma (HNSCC). Activation of the PI3K/AKT/mTOR pathway can decrease the efficiency of radiotherapy via the promotion of cell survival and DNA repair. Two PI3K inhibitors were investigated and both BKM120 and GDC0980 effectively inhibited cellular and clonogenic growth in 6 HNSCC cells, both HPV-positive as well as HPV-negative. One of the key pathways involved in resistance to therapies, including resistance to RT, is the phosphatidylinositol 3 kinase (PI3K)—protein kinase B (AKT)—mammalian target of rapamycin (mTOR) p athway[8] This pathway is involved in three main mechanism of radioresistance namely tumour cell proliferation, hypoxia and intrinsic radioresistance[9]. In this study we investigated the response to a pan PI3K inhibitor, BKM120, and a dual PI3K/mTOR inhibitor, GDC0980, in three HPV-positive and three HPV-negative HNSCC cell lines alone and in combination with RT
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