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
. 2017 Aug 9:7:170.
doi: 10.3389/fonc.2017.00170. eCollection 2017.

New Treatment Opportunities in Phosphatase and Tensin Homolog (PTEN)-Deficient Tumors: Focus on PTEN/Focal Adhesion Kinase Pathway

Roberta Alfieri  1 , Elisa Giovannetti  2   3 , Mara Bonelli  1 , Andrea Cavazzoni  1
Affiliations
Review

New Treatment Opportunities in Phosphatase and Tensin Homolog (PTEN)-Deficient Tumors: Focus on PTEN/Focal Adhesion Kinase Pathway

Roberta Alfieri et al. Front Oncol. .

Abstract

Deep genetic studies revealed that phosphatase and tensin homolog (PTEN) mutations or loss of expression are not early events in cancer development but characterize tumor progression and invasion. Loss of PTEN function causes a full activation of the prosurvival phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, but the treatment with specific inhibitors of PI3K/AKT/mTOR did not produce the expected results. One of the alternative targets of PTEN is the focal adhesion kinase (FAK) kinase, mainly involved in the control of cancer cell spread. The connection between PTEN and FAK has been demonstrated in different tumor types, with reduced PTEN activity often correlated with increased expression and phosphorylation of FAK. FAK inhibition may thus represent a promising strategy, and some clinical trials are testing FAK inhibitors alone or combined with other agents in a number of solid tumors. However, only few preclinical and clinical data described the effects of the combination of PI3K/AKT/mTOR and FAK inhibitors. Increasing knowledge on the PTEN/FAK connection could confirm PTEN as a good prognostic marker for a combination strategy based on concomitant inhibition of PI3K/AKT and FAK signaling, in advanced metastatic malignancies with altered or reduced PTEN expression.

Keywords: drug combination; focal adhesion kinase; kinase; phosphatase and tensin homolog; targeted therapy.

PubMed Disclaimer

References

    1. Stjernstrom A, Karlsson C, Fernandez OJ, Soderkvist P, Karlsson MG, Thunell LK. Alterations of INPP4B, PIK3CA and pAkt of the PI3K pathway are associated with squamous cell carcinoma of the lung. Cancer Med (2014) 3(2):337–48.10.1002/cam4.191 - DOI - PMC - PubMed
    1. Wise HM, Hermida MA, Leslie NR. Prostate cancer, PI3K, PTEN and prognosis. Clin Sci (Lond) (2017) 131(3):197–210.10.1042/CS20160026 - DOI - PubMed
    1. Perrone F, Lampis A, Orsenigo M, Di Bartolomeo M, Gevorgyan A, Losa M, et al. PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients. Ann Oncol (2009) 20(1):84–90.10.1093/annonc/mdn541 - DOI - PubMed
    1. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science (1997) 275(5308):1943–7.10.1126/science.275.5308.1943 - DOI - PubMed
    1. Wu R, Sun S, Steinberg BM. Requirement of STAT3 activation for differentiation of mucosal stratified squamous epithelium. Mol Med (2003) 9(3–4):77–84.10.2119/2003-00001.Wu - DOI - PMC - PubMed