Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Nov 22;13(11):413.
doi: 10.3390/ph13110413.

Serum and Glucocorticoid-Inducible Kinase 1 (SGK1) in NSCLC Therapy

Affiliations
Review

Serum and Glucocorticoid-Inducible Kinase 1 (SGK1) in NSCLC Therapy

Ilaria Guerriero et al. Pharmaceuticals (Basel). .

Abstract

Non-small cell lung cancer (NSCLC) remains the most prevalent and one of the deadliest cancers worldwide. Despite recent success, there is still an urgent need for new therapeutic strategies. It is also becoming increasingly evident that combinatorial approaches are more effective than single modality treatments. This review proposes that the serum and glucocorticoid-inducible kinase 1 (SGK1) may represent an attractive target for therapy of NSCLC. Although ubiquitously expressed, SGK1 deletion in mice causes only mild defects of ion physiology. The frequent overexpression of SGK1 in tumors is likely stress-induced and provides a therapeutic window to spare normal tissues. SGK1 appears to promote oncogenic signaling aimed at preserving the survival and fitness of cancer cells. Most importantly, recent investigations have revealed the ability of SGK1 to skew immune-cell differentiation toward pro-tumorigenic phenotypes. Future studies are needed to fully evaluate the potential of SGK1 as a therapeutic target in combinatorial treatments of NSCLC. However, based on what is currently known, SGK1 inactivation can result in anti-oncogenic effects both on tumor cells and on the immune microenvironment. A first generation of small molecules to inactivate SGK1 has already been already produced.

Keywords: NSCLC; SGK1; chemotherapy; immunotherapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of known serum and glucocorticoid-inducible kinases SGK1, SGK2, and SGK3 splicing variants.
Figure 2
Figure 2
Chemical structure of small molecules capable of inhibiting SGK1.

Similar articles

Cited by

References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Inamura K. Lung Cancer: Understanding Its Molecular Pathology and the 2015 WHO Classification. Front. Oncol. 2017;7:193. doi: 10.3389/fonc.2017.00193. - DOI - PMC - PubMed
    1. Travis W.D., Brambilla E., Nicholson A.G., Yatabe Y., Austin J.H.M., Beasley M.B., Chirieac L.R., Dacic S., Duhig E., Flieder D.B., et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J. Thorac. Oncol. 2015;10:1243–1260. doi: 10.1097/JTO.0000000000000630. - DOI - PubMed
    1. Kuhn E., Morbini P., Cancellieri A., Damiani S., Cavazza A., Comin C.E. Adenocarcinoma classification: Patterns and prognosis. Pathologica. 2018;110:5–11. - PubMed
    1. Park H.J., Cha Y.J., Kim S.H., Kim A., Kim E.Y., Chang Y.S. Keratinization of Lung Squamous Cell Carcinoma Is Associated with Poor Clinical Outcome. Tuberc. Respir. Dis. (Seoul) 2017;80:179–186. doi: 10.4046/trd.2017.80.2.179. - DOI - PMC - PubMed

LinkOut - more resources