Open AccessTumour-specific PI3K inhibition via nanoparticle-targeted delivery in head and neck squamous cell carcinoma
Author(s) -
Aviram Mizrachi,
Yosi Shamay,
Janki Shah,
Samuel Brook,
Joanne Soong,
Vinagolu K. Rajasekhar,
John L. Humm,
John H. Healey,
Simon N. Powell,
José Baselga,
Daniel A. Heller,
Adriana HaimovitzFriedman,
Maurizio Scaltriti
Publication year - 2017
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms14292
Subject(s) - medicine , head and neck squamous cell carcinoma , p110α , pi3k/akt/mtor pathway , cancer research , head and neck cancer , targeted therapy , cancer , cell , limiting , toxicity , radiation therapy , biology , signal transduction , microbiology and biotechnology , mechanical engineering , genetics , engineering
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.