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Volume 13
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Review

Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention

by
Nazanin Momeni Roudsari
1,
Naser-Aldin Lashgari
1,
Saeideh Momtaz
2,3,4,
Shaghayegh Abaft
1,
Fatemeh Jamali
1,
Pardis Safaiepour
1,
Kiyana Narimisa
1,
Gloria Jackson
5,
Anusha Bishayee
6,
Nima Rezaei
7,8,
Amir Hossein Abdolghaffari
1,2,3,4,* and
Anupam Bishayee
5,*
1
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran 1941933111, Iran
2
Medicinal Plants Research Center, Institute of Medicinal Plants, Academic Center for Education, Culture and Research, Tehran 1417614411, Iran
3
Toxicology and Disease Group, Pharmaceutical Sciences Research Center, Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
4
Gastrointestinal Pharmacology Interest Group, Universal Scientific Education and Research Network, Tehran 1417614411, Iran
5
Lake Erie Collage of Osteopathic Medicine, Bradenton, FL 34211, USA
6
Pine View School, Osprey, FL 34229, USA
7
Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran
8
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2021, 13(8), 1195; https://doi.org/10.3390/pharmaceutics13081195
Submission received: 28 June 2021 / Revised: 29 July 2021 / Accepted: 29 July 2021 / Published: 3 August 2021
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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Abstract

The phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of the rapamycin (mTOR)-signaling pathway has been suggested to have connections with the malignant transformation, growth, proliferation, and metastasis of various cancers and solid tumors. Relevant connections between the PI3K/Akt/mTOR pathway, cell survival, and prostate cancer (PC) provide a great therapeutic target for PC prevention or treatment. Recent studies have focused on small-molecule mTOR inhibitors or their usage in coordination with other therapeutics for PC treatment that are currently undergoing clinical testing. In this study, the function of the PI3K/Akt/mTOR pathway, the consequence of its dysregulation, and the development of mTOR inhibitors, either as an individual substance or in combination with other agents, and their clinical implications are discussed. The rationale for targeting the PI3K/Akt/mTOR pathway, and specifically the application and potential utility of natural agents involved in PC treatment is described. In addition to the small-molecule mTOR inhibitors, there are evidence that several natural agents are able to target the PI3K/Akt/mTOR pathway in prostatic neoplasms. These natural mTOR inhibitors can interfere with the PI3K/Akt/mTOR pathway through multiple mechanisms; however, inhibition of Akt and suppression of mTOR 1 activity are two major therapeutic approaches. Combination therapy improves the efficacy of these inhibitors to either suppress the PC progression or circumvent the resistance by cancer cells.
Keywords: prostate cancer; PI3K/Akt/mTOR pathway; small-molecule mTOR inhibitors; natural compounds prostate cancer; PI3K/Akt/mTOR pathway; small-molecule mTOR inhibitors; natural compounds
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MDPI and ACS Style

Roudsari, N.M.; Lashgari, N.-A.; Momtaz, S.; Abaft, S.; Jamali, F.; Safaiepour, P.; Narimisa, K.; Jackson, G.; Bishayee, A.; Rezaei, N.; et al. Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention. Pharmaceutics 2021, 13, 1195. https://doi.org/10.3390/pharmaceutics13081195

AMA Style

Roudsari NM, Lashgari N-A, Momtaz S, Abaft S, Jamali F, Safaiepour P, Narimisa K, Jackson G, Bishayee A, Rezaei N, et al. Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention. Pharmaceutics. 2021; 13(8):1195. https://doi.org/10.3390/pharmaceutics13081195

Chicago/Turabian Style

Roudsari, Nazanin Momeni, Naser-Aldin Lashgari, Saeideh Momtaz, Shaghayegh Abaft, Fatemeh Jamali, Pardis Safaiepour, Kiyana Narimisa, Gloria Jackson, Anusha Bishayee, Nima Rezaei, and et al. 2021. "Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention" Pharmaceutics 13, no. 8: 1195. https://doi.org/10.3390/pharmaceutics13081195

APA Style

Roudsari, N. M., Lashgari, N.-A., Momtaz, S., Abaft, S., Jamali, F., Safaiepour, P., Narimisa, K., Jackson, G., Bishayee, A., Rezaei, N., Abdolghaffari, A. H., & Bishayee, A. (2021). Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention. Pharmaceutics, 13(8), 1195. https://doi.org/10.3390/pharmaceutics13081195

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