Abstract PR01: Inhibitory role of phosphatidylinositol-3,4-bisphosphate in triple-negative breast cancers

Triple-negative breast cancer (lacking expression of estrogen receptor, progesterone receptor and amplification of HER2/Neu) remains one of the most aggressive subtypes, affects the youngest patients and yet still lacks an effective targeted therapy. Novel insights into the molecular mechanisms that drive these cancers are imperative to guide development and application of such targeted therapies. Data from The Cancer Genome Atlas and other sources have suggested that phospho-Akt (pAkt) levels are significantly higher in triple-negative tumors compared to either hormone receptor positive tumors (express estrogen and/or progesterone receptor) or Her2/Neu amplified tumors. This has led to the hypothesis that these tumors are dependent on phosphatidylinositide-3-kinase (PI3K) and that PI3K pathway inhibitors may be effective therapeutically in triple-negative tumors. Both PI3K-α and β are ubiquitously expressed and therefore may be important for the oncogenesis of solid tumors, including those of the breast. INPP4B catalyzes the removal of the 4' phosphate of phosphatidylinositol-(3,4)-bisphosphate creating phosphatidylinositol-(3)-phosphate. There has been debate concerning whether phosphatidylinositol-(3,4)-bisphosphate can contribute to activation of Akt and other downstream effectors, in addition to phosphatidylinositol-(3,4,5)-trisphosphate, the canonical signaling second messenger effector downstream of PI3K. If this were true, INPP4B would have a negative effec...

Source: Molecular Cancer Therapeutics - July 6, 2015 Category: Cancer & Oncology Authors: Reed, D. E., Shokat, K. M. Tags: Molecular Regulation of the PI3K-mTOR Network: Oral Presentations - Proffered Abstracts Source Type: research