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 study reveals an epigenetic mechanism associated with resistance to targeted therapy and demonstrates that therapeutic targeting of KDM6B-mediated IGFBP5 expression may provide a useful approach to mitigate both intrinsic and acquired resistance to the PI3K inhibitor in breast cancer.<i></i>.
Although it was found that AIB1 could be phosphorylated by some kinases including PI3K, the function of AIB1 and AKT interaction in breast cancer is not well defined.
Bromodomain-containing protein-4 (BRD4) has been shown to regulate the transcription of various RTK in the context of resistance to PI3K and HER2 inhibition in breast cancer models.
Antibody-mediated inhibition of this ERBB2/ERBB3/PI3K axis has been a cornerstone of treatment for ERBB2-amplified breast cancer patients for two decades.
Using a panel of small-molecule PI3K isoform-selective inhibitors in a diverse set of breast cancer cell lines, we have demonstrated that the biochemical and biological responses were highly variable and dependent on the genetic alterations present. p110alpha inhibitors were generally effective in inhibiting the phosphorylation of PKB (protein kinase B)/Akt and S6, two downstream components of PI3K signalling, in most cell lines examined.
Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel.
The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes.
Emerging evidence implies that estrogen receptor (ER) and phosphatidylinositol 3-kinase (PI3K) pathways play central roles in both breast cancer progression and response to therapy.
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.
These observations provide a strong rationale for the combined use of RSK and PI3K pathway inhibitors to elicit favorable responses in breast cancer patients with activated RSK.
LPA mediates human breast cancer MDA-BO2 cell proliferation, migration, and invasion through activation of a G(alpha i)/ERK1/2-dependent signaling pathway, whereas activation of G(alpha i)/PI3K predominates upon S1P stimulation.
Using comprehensive multi-omic molecular profiling, we assessed whether alterations or activation of the PI3K-AKT-mTOR pathway is associated with specific sites of breast cancer metastasis.<b>Experimental Design:</b> Next-generation sequencing-based whole-exome sequencing was coupled with reverse-phase protein microarray (RPPA) functional signaling network analysis to explore the PI3K-AKT-mTOR axis in 32 pretreated breast cancer metastases.
However, PI3K/Akt or p38 MAPK-specific inhibition alone partially attenuated HGF-induced COX2 and MMP-9 expression and the invasiveness of the two breast cancer cell lines, and these HGF-induced effects were almost completely abolished by simultaneous treatment with both inhibitors.
Growth factor activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway has been shown to activate the estrogen receptor (ER) alpha and to mediate tamoxifen resistance in breast cancer.
Though incidence of PI3K oncogenic mutation is prominent in breast cancer (20-30%), pharmacological targeting of this signaling pathway alone has failed to provide meaningful clinical benefit.
Adding a PI3K inhibitor to anti-estrogen receptor therapy may be a viable treatment option for women with advanced hormone receptor-positive breast cancer that becomes resistant to endocrine therapy, according to findings from the phase III BELLE-2 trial, presented at the 2015 San Antonio Breast Cancer Symposium.