Tumour-specific PI3K inhibition via nanoparticle-targeted delivery in head and neck squamous cell carcinoma Journal Article
| Authors: | Mizrachi, A.; Shamay, Y.; Shah, J.; Brook, S.; Soong, J.; Rajasekhar, V. K.; Humm, J. L.; Healey, J. H.; Powell, S. N.; Baselga, J.; Heller, D. A.; Haimovitz-Friedman, A.; Scaltriti, M. |
| Article Title: | Tumour-specific PI3K inhibition via nanoparticle-targeted delivery in head and neck squamous cell carcinoma |
| Abstract: | Alterations in PIK3CA, the gene encoding the p110α subunit of phosphatidylinositol 3-kinase (PI3Kα), are frequent in head and neck squamous cell carcinomas. Inhibitors of PI3Kα show promising activity in various cancer types, but their use is curtailed by dose-limiting side effects such as hyperglycaemia. In the present study, we explore the efficacy, specificity and safety of the targeted delivery of BYL719, a PI3Kα inhibitor currently in clinical development in solid tumours. By encapsulating BYL719 into P-selectin-targeted nanoparticles, we achieve specific accumulation of BYL719 in the tumour milieu. This results in tumour growth inhibition and radiosensitization despite the use of a sevenfold lower dose of BYL719 compared with oral administration. Furthermore, the nanoparticles abrogate acute and chronic metabolic side effects normally observed after BYL719 treatment. These findings offer a novel strategy that could potentially enhance the efficacy of PI3Kα inhibitors while mitigating dose-limiting toxicity in patients with head and neck squamous cell carcinomas. © 2017 The Author(s). |
| Journal Title: | Nature Communications |
| Volume: | 8 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2017-02-13 |
| Start Page: | 14292 |
| Language: | English |
| DOI: | 10.1038/ncomms14292 |
| PROVIDER: | scopus |
| PMCID: | PMC5316830 |
| PUBMED: | 28194032 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 March 2017 -- Source: Scopus |
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