AR Signaling and the PI3K Pathway in Prostate Cancer
Abstract
:1. Introduction
2. The Androgen Receptor Pathway
3. AR Signaling in Prostate Cancer
4. The PI3K Signaling Pathway
5. PI3K Pathway Activation in Prostate Cancer
6. Interaction of PI3K and AR Signaling
7. Therapeutic Implications
8. Combined Therapeutic Targeting of AR and PI3K Signaling
9. Biomarkers for PI3K Inhibition
10. Current Clinical Trials of PI3K Pathway Inhibitors in Prostate Cancer
11. Conclusions
Author Contributions
Conflicts of Interest
References
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Agent | Pharmaceutical Company | Sponsor | Trial | Endpoint | Patient Population | Status | Biomarkers |
---|---|---|---|---|---|---|---|
BKM120 (PI3K) | Novartis | Duke University | Phase II, BKM120 in mCRPC (NCT01385293) | PFS | Post chemo; prior sipuleucel-T, abiraterone (Abi), or enzalutamide (enza) allowed. n = 66 | Study accrued, results awaited | Circulating tumor cells (CTCs), Tissue PI3K signature, PTEN status, PI3K activation, PSA levels |
University of California | Phase II, neoadjuvant BKM120 for high-risk prostate cancer pre radical prostatectomy (RP) (NCT01695473) | PI3K inhibition in tumor measured by IHC | Candidates for RP; high risk defined by trial Target n = 24 | Study accrued, results awaited | IHC for phosphorylation of: S6, 4EBP1, or AKT | ||
GSK2636771 (PI3K) | GlaxoSmithKline | GSK | Phase I, GSK2636771 in combination with Enza for mCRPC (NCT02215096) | Safety and tolerability | PTEN deficient tumors post progression on Enza n = 44 | Recruiting | PTEN status PSA levels |
AZD8186 (PI3K) | AstraZeneca | AZ | Phase I, AZD8186 +/− Abi or AZD2014 in TNBC/NSCLC or CRPC or known PTEN-deficient/PI3 mutated disease (NCT01884285) | Safety and tolerability | mCRPC (Total) Target n = 180 | Recruiting | PSA levels |
LY3023414 (PI3K + mTOR) | Eli Lilly | Eli Lilly | Phase II Study of Enzalutamide +/− LY3023414 in mCRPC (NCT02407054) | PFS | mCRPC post progression on Abi; no prior chemo in castrate-refractory setting, immunotherapy, or Ra223 Target n = 144 | Recruiting | PSA levels |
AZD5363 (AKT) | AstraZenica | Institute of Cancer Research, UK | Phase I/II, Enza +/− AZD5363 in mCRPC | Phase II: Best overall tumor response | mCRPC with tissue for PTEN testing Target n = 136 | Recruiting | PTEN PSA levels |
University Hospital Southampton NHS Foundation Trust | Randomised Phase II, Docetaxel +/− AZD 5363 in mCRPC | PFS | Chemotherapy-naïve mCRPC | Recruiting | PSA levels | ||
MK2206 (AKT) | Merck | National Cancer Institute | Phase II, bicalutamide +/− MK2206 in men with HSPC | Proportion undetectable PSA | Biochemically relapsed hormone-sensitive PC following definitive treatment n = 104 | Study accrued, results awaited | PSA levels |
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Crumbaker, M.; Khoja, L.; Joshua, A.M. AR Signaling and the PI3K Pathway in Prostate Cancer. Cancers 2017, 9, 34. https://doi.org/10.3390/cancers9040034
Crumbaker M, Khoja L, Joshua AM. AR Signaling and the PI3K Pathway in Prostate Cancer. Cancers. 2017; 9(4):34. https://doi.org/10.3390/cancers9040034
Chicago/Turabian StyleCrumbaker, Megan, Leila Khoja, and Anthony M. Joshua. 2017. "AR Signaling and the PI3K Pathway in Prostate Cancer" Cancers 9, no. 4: 34. https://doi.org/10.3390/cancers9040034
APA StyleCrumbaker, M., Khoja, L., & Joshua, A. M. (2017). AR Signaling and the PI3K Pathway in Prostate Cancer. Cancers, 9(4), 34. https://doi.org/10.3390/cancers9040034