It has been demonstrated that the PI3K pathway is inappropriately activated in BRCA1-deficient breast cancers which can be downregulated by microRNA 451 (miR-451).
We investigated whether mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with response to neoadjuvant human epidermal growth factor receptor 2 (HER2) -targeted therapies in patients with breast cancer.
We aimed to assess the safety and identify the recommended phase 2 dose of the PARP inhibitor olaparib in combination with the PI3K inhibitor alpelisib in patients with epithelial ovarian cancer and in patients with breast cancer.
Our results suggest that PI3K inhibitors should target both p110alpha and p110beta catalytic subunits, whether wild-type or mutant, and be combined with endocrine therapy for maximal efficacy when treating ER(+) breast cancer.
The phosphoinositide-3-kinase (PI3K) pathway is commonly deregulated in breast cancer through several mechanisms, including PIK3CA mutation and loss of phosphatase and tensin homolog (PTEN) and inositol polyphosphate 4-phosphatase-II (INPP4B).
Phosphatidylinositol 3-kinase (PI3K) pathway activation has been suggested to negatively influence response to anti-HER2 therapy in breast cancer patients.
Therefore, the present review attempts to address the implication of key enzymes of the aerobic glycolytic pathway including hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK), glucose transporters (GLUTs), together with related signaling pathways including protein kinase B(PI3K/AKT), mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) and transcription factors (c-myc, p53 and HIF-1) in the research of BC.
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.
Association of PI3K Pathway Mutations with Early Positron-Emission Tomography/CT Imaging Response after Radioembolization for Breast Cancer Liver Metastases: Results of a Single-Center Retrospective Pilot Study.
Furthermore, our findings show that triple negative breast cancers with apocrine differentiation constitute a distinct subset, characterized by a high frequency of PI3K pathway alterations similar to luminal subtypes of breast cancer.
Overall, our findings suggest SIK2 as a potential tumor suppressor in the control of breast tumorigenesis, at least in part, <i>via</i> inhibiting PI3K/Akt and Ras/ERK signaling cascades simultaneously and a novel prognostic marker, especially in basal subtypes of breast cancer.
Here, we review alterations in the PI3K pathway in breast cancer, their association with therapeutic resistance, and the state of clinical development of PI3K pathway inhibitors.
For instance, the PI3K/Akt pathway, which is impeded by luteolin, has several downstream programs involved in increased proliferation, survival, and metastatic potential in breast cancer.
Our findings demonstrate that epoxyazadiradione inhibits PI3K/Akt-dependent mitochondrial depolarisation, induces apoptosis and attenuates cell migration, angiogenesis and breast tumor growth suggesting that this compound may act as a potent therapeutic agent for the management of breast cancer.
Phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway activation in patients with HER2-positive (HER2(+)) breast cancer has been implicated in de novo and acquired trastuzumab resistance.
The elevated expression of TGF-β1 increases the PI3K/AkT/mTOR activity in human breast cancer tissue and potentially motivates tumor metastasis and resistance to chemotherapy.
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.
Previous work has shown that prostate cancer in a Pten-null murine model is dependent on the p110β isoform of phosphatidylinositol 3-kinase (PI3K), while breast cancer driven by either polyoma middle T antigen (MT) or HER2 is p110α dependent.