Strategically timing inhibition of phosphatidylinositol 3-kinase to maximize therapeutic index in estrogen receptor alpha-positive, PIK3CA-mutant breast cancer Authors

نویسندگان

  • Wei Yang
  • Sarah R. Hosford
  • Lloye M. Dillon
  • Kevin Shee
  • Stephanie C. Liu
  • Jennifer R. Bean
  • Laurent Salphati
  • Jodie Pang
  • Xiaolin Zhang
  • Michelle A. Nannini
  • Eugene Demidenko
  • Darcy Bates
  • Lionel D. Lewis
  • Jonathan D. Marotti
  • Alan R. Eastman
  • Todd W. Miller
چکیده

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Strategically Timing Inhibition of Phosphatidylinositol 3-Kinase to Maximize Therapeutic Index in Estrogen Receptor Alpha-Positive, PIK3CA-Mutant Breast Cancer.

PURPOSE Phosphatidylinositol 3-kinase (PI3K) inhibitors are being developed for the treatment of estrogen receptor α (ER)-positive breast cancer in combination with antiestrogens. Understanding the temporal response and pharmacodynamic effects of PI3K inhibition in ER(+) breast cancer will provide a rationale for treatment scheduling to maximize therapeutic index. EXPERIMENTAL DESIGN Antiestr...

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The phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene is frequently mutated in breast cancer (BCa). Sex hormone receptors (HRs), including estrogen receptor (ER) and progesterone receptor (PR) play pivotal roles in BCa. In this study, we evaluated the association between PIK3CA mutations and ER/PR expression and the prognostic role of PIK3CA mutations in BCa...

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PIK3CA and PIK3CB inhibition produce synthetic lethality when combined with estrogen deprivation in estrogen receptor-positive breast cancer.

Several phosphoinositide 3-kinase (PI3K) catalytic subunit inhibitors are currently in clinical trial. We therefore sought to examine relationships between pharmacologic inhibition and somatic mutations in PI3K catalytic subunits in estrogen receptor (ER)-positive breast cancer, in which these mutations are particularly common. RNA interference (RNAi) was used to determine the effect of selecti...

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تاریخ انتشار 2015