While TP53 mutation and MYC amplification were synergistic in promoting tumor progression, PIK3CA mutation was found to have alleviated the oncogenic effect of either the TP53 mutation or MYC amplification, and was associated with a significant reduction in mitotic activity in TP53 mutated and/or MYC amplified breast cancer.
While the PI3K/AKT/mTOR pathway is known to be an important growth pathway in HR positive breast cancer, PI3K inhibitors have been disappointing due to modest effect sizes and significant toxicity.
Western blot analysis data indicate that MAPK/ERK and PI3K/Akt signaling in breast cancer cells with high ER-α36 expression are mediated by ER-α36, and are inhibited by pterostilbene.
We used pharmacogenomic analysis of a large panel of breast cancer cell lines with detailed accompanying molecular information to identify molecular predictors of response to a potent and selective inhibitor of MEK and also to define molecular mechanisms underlying combined MEK and PI3K targeting in basal-like breast cancer.
We used a large panel of breast cancer cell lines and in vivo xenograft models to identify candidate predictive biomarkers for a selective inhibitor of class I PI3K that is currently in clinical development.
We suggest that PIK3CA is significant in breast tumorigenesis serve as a prevalent mechanism contributes to the oncogenic activation pathway of PIK3CA in breast cancer.
We studied the interactions between ERα and Src or PI3K by proximity ligation assay (PLA) in in-vitro and in-vivo endocrine therapy-resistant breast cancer models.
We sought to discover predictive biomarker for the efficacy of BYL719 by dissecting the proliferative signaling pathway mediated by PI3K in breast cancer.
We show that serum and glucocorticoid-regulated kinase 3 (SGK3) is amplified in breast cancer and activated downstream of PIK3CA in a manner dependent on the phosphoinositide phosphatase INPP4B.
We report here that the combination of a PI3K inhibitor with a PARP inhibitor provides in vivo synergy for treatment of an endogenous mouse model for BRCA1-related breast cancers, making this a candidate combination to be tested in human clinical trials.
We propose that PCR-HRM and PCR-ARMS can be combined for the cost-effective routine clinical identification of PIK3CA mutations for the purpose of personalizing therapy for invasive breast cancers.
We propose that addition of BH3 mimetics offers a therapeutic strategy to markedly improve the cytotoxic activity of PI3Ki in hormonal therapy-resistant and ER-independent PIK3CA-mutant breast cancer.
We previously reported that combining a phosphoinositide 3-kinase (PI3K) inhibitor with a poly-ADP Rib polymerase (PARP)-inhibitor enhanced DNA damage and cell death in breast cancers that have genetic aberrations in BRCA1 and TP53.
We performed next generation whole exon sequencing of TP53 and PIK3CA genes, which are the 2 most common genetic alterations in breast cancer, in plasma DNA (pDNA) of 17 metastatic breast cancer (MBC) patients and in tumor DNA (tDNA) from their primary tumors.
We identified intergenic fusions involving driver genes, including <i>PIK3CA, AKT3, RAF1</i>, and <i>ESR1</i>, in 14% (24/173) of unselected patients with advanced HR<sup>+</sup> breast cancer.
We identified a number of predicted driver mutations (including PIK3CA and TP53) that were acquired during transformation of non-malignant MCF10A cells to their malignant counterparts that are also present in analysed primary breast cancers from The Cancer Genome Atlas (TCGA).
We hypothesized that the phosphoinositide 3-kinase (PI3K)/AKT pathway and the expression of related miRNAs are involved in the chemotherapeutic activities of mango polyphenolics in a mouse xenograft model for breast cancer.
We have previously shown that methylation of ERα is required for the formation of the ERα/Src/PI3K complex and that ERα is hypermethylated in a subset of breast cancers.
We have previously reported that the PI3K pathway regulates estrogen receptor (ER)-dependent transcription in breast cancer through the phosphorylation of the lysine methyltransferase KMT2D by AKT.
We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where tandem mass spectrometry detected and quantitatively measured the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K activation.
We firstly provided evidence that LHX6 exerted its anti-tumor function on BC via suppressing activation of the PI3K/Akt/mTOR signaling, which eventually inhibited the progression of BC.
We decided to investigate the association of PIK3CA mutations with pathologic features and clinical outcome in a large series of patients with breast cancer.
We conclude that 9p21.3 (CDKN2A) loss and PIK3CA mutation characterize a subgroup of metaplastic breast cancers with myoepithelial and spindle cell differentiation.