Tumour-specific PI3K inhibition via nanoparticle-targeted delivery in head and neck squamous cell carcinoma.
Nat Commun
; 8: 14292, 2017 02 13.
Article
em En
| MEDLINE
| ID: mdl-28194032
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
/
Carcinoma de Células Escamosas
/
Ensaios Antitumorais Modelo de Xenoenxerto
/
Nanopartículas
/
Classe I de Fosfatidilinositol 3-Quinases
/
Neoplasias de Cabeça e Pescoço
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos