As miR-221 targets several regulators of the PI3K-AKT-mTOR pathway and a link between this pathway and CD44 has been previously shown in prostate cancer, we considered miR-221 regulation of CD44 may be through this pathway.
We compared the involvement of PI3K/PTEN/Akt signaling in the regulation of the cell-cycle regulator p27(kip1) and investigated the mechanism of PI3K/PTEN/Akt modulation of p27(kip1) in the prostate cancer cell lines LNCaP, PC346, PC3, and DU145.
Developing combination therapy for castrate-resistant prostate cancer (CRPC) may require exploiting new drug targets outside androgen receptor and PI3K / AKT / mTOR signal transduction pathways implicated in prostate cancer (PCa) progression.
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays important roles for prostate cancer cell survival, and the androgen receptor (AR) plays essential roles for prostate cancer cell proliferation.
Increased p110beta expression in PCa may be required for RTK-independent PI3K pathway activation in adult prostate epithelium with genetic or epigenetic PTEN down-regulation.
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.
Taken together, these results suggest that aberrant activation of PI3K-Akt pathway may contribute to increased cell invasiveness and facilitate prostate cancer progression.
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.
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.
In addition, genetic deletion of 4E-BP1 and 4E-BP2 significantly accelerates all phases of cancer development in the context of PTEN loss-driven prostate cancer in mice despite potent PI3K/AKT and mTOR activation.
Our findings suggest that combined targeting of both the AR/α6β1 and PI3K pathways may effectively trigger prostate cancer cell death, enhancing the potential therapeutic value of PI3K inhibitors being evaluated in this setting.
Together, our data suggest a new approach for the treatment of prostate cancer by targeting both tumor cells and tumor microenvironment with PI3Kα/β/δ inhibitor.<i></i>.
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.