PTEN, (10q23.3), is a negative regulator of the phosphatidylinositol 3-kinase (PIK3)/AKT survival pathway and a tumor suppressor frequently deleted in PCa.
Inhibition of AKT with a pharmacologic inhibitor also induced apoptosis when combined with antiandrogens, consistent with recent evidence for PI3K and AR pathway crosstalk in prostate cancer cells.
These results suggest that the combination of a PI3K inhibitor and a PSMA-targeted protein synthesis inhibitor toxin represents a promising novel strategy for advanced prostate cancer therapy that should be further investigated.
Previous work has shown that there is reciprocal feedback regulation of PI3K and AR signaling in PCa, suggesting that cotargeting both pathways may enhance therapeutic efficacy.
Interestingly, both PTEN rescue and phosphoinositide 3-kinase (PI3K) inhibitor LY294002 treatment increase the PLZF expression in prostate cancer cell lines.
We identified differential therapeutic vulnerabilities that emerge upon the loss of both PTEN and p53, and observed that combined inhibition of PARP and PI3K provides increased efficacy in hormone-insensitive advanced prostate cancer.
It is anticipated that through an improved understanding of the biology of the PI3K/Akt pathway in prostate cancer, relevant biomarkers and rationale combination therapies will optimize targeting of this pathway to improve outcomes among patients with aggressive prostate cancer.
Disruption of FoxO activity due to loss of phosphatase and tensin homolog and activation of phosphatidylinositol-3 kinase (PI3K)/Akt are frequently observed in prostate cancer.
The findings from this study suggest that the combination of dual PI3K/Akt/mTOR inhibitors (BEZ235 or PI103) with radiotherapy is a promising modality for the treatment of CaP to overcome radioresistance.
ERG/AR overexpression status characterized 152 genes signatures including WNT, PI3K/AKT and chemokine signaling pathways known to be deregulated in PCa.
A novel PI3K inhibitor displays potent preclinical activity against an androgen-independent and PTEN-deficient prostate cancer model established from the cell line PC3.
To demonstrate that the PTEN/PI3K/Akt/NF-κB pathway plays an important role in regulating the prostate cancer stem-like cell population by upregulating ABCG2.
Based on our findings, we conclude that the PTEN/PI3K/Akt pathway is critical for prostate cancer survival, and targeting PI3K signaling by NVP-BEZ235 may be beneficial in the treatment of prostate cancer, independent of the PTEN genotype.
Increased 4EBP1 abundance was a common feature in prostate cancer patients who had been treated with the PI3K pathway inhibitor BKM120; thus, 4EBP1 may be associated with drug resistance in human tumors.
Electroporation was performed to introduce linear regulatory plasmid PrevTet-off-in and conjugative plasmid PrevTRE2-flag-E6AP into prostate cancer cell line to establish wild-type E6-AP over-expressing transgenic LNCaP cell line; Western blot assay was adopted to examine expression levels of E6-AP, mammalian target of rapamycin (mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K); PI3K inhibitor LY294002 was applied to all the cells and MTT assay was used to measure cell proliferation; Matrigel invasion chamber assay was adopted to detect cancer cell migration and invasion.