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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MSK Authors
  1. Simon Nicholas Powell
    165 Powell
  2. John Laurence Humm
    339 Humm
  3. John H Healey
    374 Healey
  4. Daniel Alan Heller
    44 Heller
  5. Jose T Baselga
    394 Baselga
  6. Samuel Ian Brook
    5 Brook
  7. Janki Kalpesh Shah
    13 Shah
  8. Yosef   Shamay
    11 Shamay
  9. Joanne Soong
    3 Soong