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The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling

The European Cancer Stem Cell Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, Wales, UK
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(12), 4507; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124507
Received: 1 June 2020 / Revised: 22 June 2020 / Accepted: 22 June 2020 / Published: 25 June 2020
(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)
Oncogenic activation of the phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB/AKT), and mammalian target of rapamycin (mTOR) pathway is a frequent event in prostate cancer that facilitates tumor formation, disease progression and therapeutic resistance. Recent discoveries indicate that the complex crosstalk between the PI3K-AKT-mTOR pathway and multiple interacting cell signaling cascades can further promote prostate cancer progression and influence the sensitivity of prostate cancer cells to PI3K-AKT-mTOR-targeted therapies being explored in the clinic, as well as standard treatment approaches such as androgen-deprivation therapy (ADT). However, the full extent of the PI3K-AKT-mTOR signaling network during prostate tumorigenesis, invasive progression and disease recurrence remains to be determined. In this review, we outline the emerging diversity of the genetic alterations that lead to activated PI3K-AKT-mTOR signaling in prostate cancer, and discuss new mechanistic insights into the interplay between the PI3K-AKT-mTOR pathway and several key interacting oncogenic signaling cascades that can cooperate to facilitate prostate cancer growth and drug-resistance, specifically the androgen receptor (AR), mitogen-activated protein kinase (MAPK), and WNT signaling cascades. Ultimately, deepening our understanding of the broader PI3K-AKT-mTOR signaling network is crucial to aid patient stratification for PI3K-AKT-mTOR pathway-directed therapies, and to discover new therapeutic approaches for prostate cancer that improve patient outcome. View Full-Text
Keywords: AKT; AR; castration-resistant prostate cancer (CRPC); MAPK; mTOR; PI3K; prostate cancer; therapeutic resistance; WNT AKT; AR; castration-resistant prostate cancer (CRPC); MAPK; mTOR; PI3K; prostate cancer; therapeutic resistance; WNT
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MDPI and ACS Style

Shorning, B.Y.; Dass, M.S.; Smalley, M.J.; Pearson, H.B. The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling. Int. J. Mol. Sci. 2020, 21, 4507. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124507

AMA Style

Shorning BY, Dass MS, Smalley MJ, Pearson HB. The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling. International Journal of Molecular Sciences. 2020; 21(12):4507. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124507

Chicago/Turabian Style

Shorning, Boris Y., Manisha S. Dass, Matthew J. Smalley, and Helen B. Pearson 2020. "The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling" International Journal of Molecular Sciences 21, no. 12: 4507. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124507

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