Targeting PI3K/AKT/mTOR Signaling Pathway in Breast Cancer

doi:10.3390/cancers13143517

Review

. 2021 Jul 14;13(14):3517.

doi: 10.3390/cancers13143517.

Targeting PI3K/AKT/mTOR Signaling Pathway in Breast Cancer

Huayi Li¹, Lorenzo Prever¹, Emilio Hirsch¹, Federico Gulluni¹

Affiliations

PMID: 34298731
PMCID: PMC8304822
DOI: 10.3390/cancers13143517

Review

Targeting PI3K/AKT/mTOR Signaling Pathway in Breast Cancer

Huayi Li et al. Cancers (Basel). 2021.

. 2021 Jul 14;13(14):3517.

doi: 10.3390/cancers13143517.

Authors

Huayi Li¹, Lorenzo Prever¹, Emilio Hirsch¹, Federico Gulluni¹

Affiliation

¹ Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy.

PMID: 34298731
PMCID: PMC8304822
DOI: 10.3390/cancers13143517

Abstract

Breast cancer is the most frequently diagnosed cancer and the primary cause of cancer death in women worldwide. Although early diagnosis and cancer growth inhibition has significantly improved breast cancer survival rate over the years, there is a current need to develop more effective systemic treatments to prevent metastasis. One of the most commonly altered pathways driving breast cancer cell growth, survival, and motility is the PI3K/AKT/mTOR signaling cascade. In the past 30 years, a great surge of inhibitors targeting these key players has been developed at a rapid pace, leading to effective preclinical studies for cancer therapeutics. However, the central role of PI3K/AKT/mTOR signaling varies among diverse biological processes, suggesting the need for more specific and sophisticated strategies for their use in cancer therapy. In this review, we provide a perspective on the role of the PI3K signaling pathway and the most recently developed PI3K-targeting breast cancer therapies.

Keywords: AKT; PI3K; breast cancer; class II PI3K; clinical trial; inhibitor; mTOR; metastasis.

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Conflict of interest statement

E.H. is a co-founder of Kither Biotech, a company involved in the development of PI3K inhibitors. The other authors declare no conflict of interest.

Figures

**Figure 1**
Signaling by the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) pathway and the respective inhibitors.

See this image and copyright information in PMC

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References

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1. Maehama T., Dixon J.E. The Tumor Suppressor, PTEN/MMAC1, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3,4,5-Trisphosphate. J. Biol. Chem. 1998;273:13375–13378. doi: 10.1074/jbc.273.22.13375. - DOI - PubMed
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[1] Bilanges B., Posor Y., Vanhaesebroeck B. PI3K isoforms in cell signalling and vesicle trafficking. Nat. Rev. Mol. Cell Biol. 2019;20:515–534. doi: 10.1038/s41580-019-0129-z. - DOI - PubMed

[2] Bilanges B., Posor Y., Vanhaesebroeck B. PI3K isoforms in cell signalling and vesicle trafficking. Nat. Rev. Mol. Cell Biol. 2019;20:515–534. doi: 10.1038/s41580-019-0129-z. - DOI - PubMed

[3] Gulluni F., De Santis M.C., Margaria J.P., Martini M., Hirsch E. Class II PI3K Functions in Cell Biology and Disease. Trends Cell Biol. 2019;29:339–359. doi: 10.1016/j.tcb.2019.01.001. - DOI - PubMed

[4] Gulluni F., De Santis M.C., Margaria J.P., Martini M., Hirsch E. Class II PI3K Functions in Cell Biology and Disease. Trends Cell Biol. 2019;29:339–359. doi: 10.1016/j.tcb.2019.01.001. - DOI - PubMed

[5] Hirsch E., Gulluni F., Martini M. Phosphoinositides in cell proliferation and metabolism. Adv. Biol. Regul. 2020;75:100693. doi: 10.1016/j.jbior.2020.100693. - DOI - PubMed

[6] Hirsch E., Gulluni F., Martini M. Phosphoinositides in cell proliferation and metabolism. Adv. Biol. Regul. 2020;75:100693. doi: 10.1016/j.jbior.2020.100693. - DOI - PubMed

[7] Maehama T., Dixon J.E. The Tumor Suppressor, PTEN/MMAC1, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3,4,5-Trisphosphate. J. Biol. Chem. 1998;273:13375–13378. doi: 10.1074/jbc.273.22.13375. - DOI - PubMed

[8] Maehama T., Dixon J.E. The Tumor Suppressor, PTEN/MMAC1, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3,4,5-Trisphosphate. J. Biol. Chem. 1998;273:13375–13378. doi: 10.1074/jbc.273.22.13375. - DOI - PubMed

[9] Geering B., Cutillas P.R., Nock G., Gharbi S.I., Vanhaesebroeck B. Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers. Proc. Natl. Acad. Sci. USA. 2007;104:7809–7814. doi: 10.1073/pnas.0700373104. - DOI - PMC - PubMed

[10] Geering B., Cutillas P.R., Nock G., Gharbi S.I., Vanhaesebroeck B. Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers. Proc. Natl. Acad. Sci. USA. 2007;104:7809–7814. doi: 10.1073/pnas.0700373104. - DOI - PMC - PubMed

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Targeting PI3K/AKT/mTOR Signaling Pathway in Breast Cancer

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Targeting PI3K/AKT/mTOR Signaling Pathway in Breast Cancer

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Conflict of interest statement

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