Blockade Efficacy of MEK/ERK-Dependent Autophagy Enhances PI3K/Akt Inhibitor NVP-BKM120's Therapeutic Effectiveness in Lung Cancer Cells

Ren, Hui; Chen, Mingwei

doi:10.1016/j.chest.2016.02.314

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2020

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“…The low clinical durability and resistance to PI3K inhibitors have repeatedly been reported in literature 14 . The activation of rescue pathways can be a part of the answer to this 44,45,65,66 . In addition, the half maximum inhibitory concentration (IC50) of BKM120 to fully block all PI3K forms as monotherapy is high, leading to cellular toxicity via disrupting microtubule dynamics 11,21,67,68 .…”

Section: Discussionmentioning

confidence: 99%

The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells

Glorieux

Dok

Nuyts

2020

Sci Rep

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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.

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