期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/ncomms14292
关键词
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资金
- Cancer Center Support Grant [P30 CA008748]
- NIH Director's New Innovator Award [DP2-HD075698]
- New York State Department of Health [DOH01-C30315GG-3450000]
- Center for Experimental Therapeutics of Memorial Sloan Kettering Cancer Center
- Commonwealth Foundation for Cancer Research
- Anna Fuller Fund
- Louis V. Gerstner Jr Young Investigator's Fund
- Frank A. Howard Scholars Programme
- Imaging and Radiation Sciences Programme
- Center for Metastasis Research at Memorial Sloan Kettering Cancer Center
- Center for Metastasis Research Scholars Fellowship Programme
Alterations in PIK3CA, the gene encoding the p110 alpha subunit of phosphatidylinositol 3-kinase (PI3K alpha), are frequent in head and neck squamous cell carcinomas. Inhibitors of PI3K alpha 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 PI3K alpha 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 PI3K alpha inhibitors while mitigating dose-limiting toxicity in patients with head and neck squamous cell carcinomas.
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