Interestingly, both PTEN rescue and phosphoinositide 3-kinase (PI3K) inhibitor LY294002 treatment increase the PLZF expression in prostate cancer cell lines.
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.
Multiple pathway analysis of clinical prostate cancer (PCa) studies showed increased AR activity in hyperplasia and primary PCa but variable AR activity in castrate resistant (CR) PCa, loss of TGFβ activity in PCa, increased Wnt activity in TMPRSS2:ERG fusion protein-positive PCa, active PI3K pathway in advanced PCa, and active PI3K and NFκB as potential hormonal resistance pathways.
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.
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.
Our previous studies demonstrated that the class IA PI3K/p110β is critical in castration-resistant progression of prostate cancer (CRPC) and that targeting prostate cancer with nanomicelle-loaded p110β-specific inhibitor TGX221 blocked xenograft tumor growth in nude mice, confirming the feasibility of p110β-targeted therapy for CRPCs.
Our results suggest that TGFBR1 and PI3K could be used as useful biomarkers for early diagnosis and prognoses for biochemical recurrence in prostate cancer after radical prostatectomy.
Over-activation of phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is one of important mechanisms to promote castration resistant prostate cancer, the final stage of prostate cancer (PCa).
Phosphatase and tensin homolog (PTEN) deleted on chromosome 10, a tumor suppressor that negatively regulates the phosphoinositide-3-kinase(PI3K) which has been implicated in a number of human malignancies including prostate cancer.
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.
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.