Aberrations in the phosphoinositide-3-kinase (PI3K) and mitogen-activated protein kinase pathways have been linked to increased breast cancer proliferation and survival.
The purpose of this study was to retrospectively investigate the response to trastuzumab in breast cancer patients in terms of the potential roles of several oncogenic pathways (phosphatase and tensin homolog (PTEN) and phosphatidylinositol 3-kinase (PI3K)) in relation to HER2 status.
Antibody-mediated inhibition of this ERBB2/ERBB3/PI3K axis has been a cornerstone of treatment for ERBB2-amplified breast cancer patients for two decades.
<b>Introduction</b>: Activation of phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathways occurs in 70% of breast cancer, including PIK3CA activating mutations, PTEN loss and AKT mutation.
Furthermore, GSK3β can regulate cell viability through the PTEN/PI3K/AKT signaling pathway and induce chemoresistance, serving as a valuable molecular strategy for breast cancer therapy.
These exploratory analyses of a prospective trial in luminal breast cancer suggest high CD8 infiltration is associated with unfavorable outcome and that PI3K pathway alterations might be associated with the composition of the tumor microenvironment.
Contrarily, the finding for the MTOR gene and breast cancer is biologically plausible because the MTOR protein plays an important role in PI3K/Akt signaling, which is a pathway related to cancer development and cell senescence.
We analyzed cancer-specific biclusters and found that the PI3K/Akt signaling pathway is strongly enriched with targets of a few miRNAs in breast cancer and diffuse large B-cell lymphoma.
Our studies demonstrated that MAP2K4 has the potential to serve as an oncogene in breast cancer and it activates the phosphorylated PI3K/AKT signaling pathway to activate downstream cycle-associated proteins and EMT signals while interacting with Vimentin to promote breast cancer cells proliferation, migration, and invasion.
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.
Furthermore, DT-13 decreased PLOD2 expression through modulating JAK/STAT3 and PI3K/AKT signaling pathways directly or indirectly in the adipocyte-breast cancer microenvironment.
3-phosphoinositide dependent protein kinase-1 (PDK1), a transducer protein that functions downstream of PI3K, is responsible for the regulation of cell proliferation and migration and it also has been found to play a key role in different cancers, pancreatic and breast cancer amongst others.
The results of this study suggest that the brain-penetrant PI3K/mTOR targeting GDC-0084 is a promising treatment option for breast cancer brain metastases with dysregulated PI3K/mTOR signaling pathway conferred by activating <i>PIK3CA</i> mutations.
Together, our findings highlight a novel role of BTF3 in modulation of ERα-dependent transcriptional activity and its potential as a predictive marker for the response to PI3K-targeted therapy in ER + breast cancer.
High CapG level also significantly correlated with shorter relapse-free survival as well as hyper-activation of PI3K/Akt signaling in breast cancer patients.
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.