Combined inhibition of PI3K and PARP has been shown to be effective in the treatment of preclinical models of breast cancer and prostate cancer independent of BRCA or PIK3CA mutational status.
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.
Because the major reason for the limited efficacy of PI3K/Akt-targeted therapies in prostate cancer (PCa) is loss of mTOR-regulated feedback suppression, it is therefore important to assess the functional importance and regulation of GRB10 under these conditions.
The p110β isoform of PI3K plays a particularly important role in the pathogenesis of prostate cancer, but the origin of its activation was so far unknown.
On the basis of our previous work defining the molecular rationale for combined targeting of the PI3K and AR pathways in <i>PTEN</i> loss prostate cancer, the first clinical trial was recently reported demonstrating a significant benefit for combination therapy in patients with metastatic prostate cancer.
In summary, we identify ARID4B as a master regulator in the PTEN-PI3K pathway, thus providing a potential therapeutic target for prostate cancer carrying PTEN mutations.
Taken together, these results indicate that ST6Gal-I plays a critical role in cell proliferation and invasion via the PI3K/Akt/GSK-3β/β-catenin signaling pathway during PCa progression and that it might be a promising target for PCa prognosis determination and therapy.
Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls.
The data suggest that PI3K/Akt-NF-kappaB axis may promote PC bone metastasis in part by regulating transcription and activation of the BMP-2-Smad signaling cascade in osteotropic PC cells.
The Sex-determining region Y-box 4 and homeobox C6 transcriptional networks in prostate cancer progression: crosstalk with the Wnt, Notch, and PI3K pathways.
Interestingly, both PTEN rescue and phosphoinositide 3-kinase (PI3K) inhibitor LY294002 treatment increase the PLZF expression in prostate cancer cell lines.
Selected compounds were tested for potential PI3Kα inhibitory activity as well as for their cytotoxic effect in prostate cancer cell lines (DU145 and PC3).