PTEN in Lung Cancer: Dealing with the Problem, Building on New Knowledge and Turning the Game Around
Anastasios Gkountakos 1, Giulia Sartori 2
, Italia Falcone 3, Geny Piro 4,5, Ludovica Ciuffreda 6, Carmine Carbone 4,5, Giampaolo Tortora 4,5, Aldo Scarpa 1,7, Emilio Bria 4,5, Michele Milella 2, Rafael Rosell 8, Vincenzo Corbo 1,7,* and Sara Pilotto 2,*
, Italia Falcone 3, Geny Piro 4,5, Ludovica Ciuffreda 6, Carmine Carbone 4,5, Giampaolo Tortora 4,5, Aldo Scarpa 1,7, Emilio Bria 4,5, Michele Milella 2, Rafael Rosell 8, Vincenzo Corbo 1,7,* and Sara Pilotto 2,*
1
Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy
2
Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, 37134 Verona, Italy
3
Medical Oncology 1, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy
4
Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
5
Medical Oncology, Università Cattolica Del Sacro Cuore, 00168 Rome, Italy
6
SAFU Laboratory, Department of Research, Advanced Diagnostics, and Technological Innovation, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy
7
Center for Applied Research on Cancer (ARC-NET), University of Verona, 37134 Verona, Italy
8
Germans Trias i Pujol, Health Sciences Institute and Hospital, Campus Can Ruti, 08916 Badalona, Spain
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(8), 1141; https://doi.org/10.3390/cancers11081141
Received: 24 June 2019 / Revised: 27 July 2019 / Accepted: 29 July 2019 / Published: 9 August 2019
(This article belongs to the Special Issue PTEN: A Multifaceted Tumor Suppressor)
Abstract
Lung cancer is the most common malignancy and cause of cancer deaths worldwide, owing to the dismal prognosis for most affected patients. Phosphatase and tensin homolog deleted in chromosome 10 (PTEN) acts as a powerful tumor suppressor gene and even partial reduction of its levels increases cancer susceptibility. While the most validated anti-oncogenic duty of PTEN is the negative regulation of the PI3K/mTOR/Akt oncogenic signaling pathway, further tumor suppressor functions, such as chromosomal integrity and DNA repair have been reported. PTEN protein loss is a frequent event in lung cancer, but genetic alterations are not equally detected. It has been demonstrated that its expression is regulated at multiple genetic and epigenetic levels and deeper delineation of these mechanisms might provide fertile ground for upgrading lung cancer therapeutics. Today, PTEN expression is usually determined by immunohistochemistry and low protein levels have been associated with decreased survival in lung cancer. Moreover, available data involve PTEN mutations and loss of activity with resistance to targeted treatments and immunotherapy. This review discusses the current knowledge about PTEN status in lung cancer, highlighting the prevalence of its alterations in the disease, the regulatory mechanisms and the implications of PTEN on available treatment options. View Full-TextKeywords:
PTEN; lung cancer; NSCLC; genetic; epigenetic; treatment resistance; survival
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MDPI and ACS Style
Gkountakos, A.; Sartori, G.; Falcone, I.; Piro, G.; Ciuffreda, L.; Carbone, C.; Tortora, G.; Scarpa, A.; Bria, E.; Milella, M.; Rosell, R.; Corbo, V.; Pilotto, S. PTEN in Lung Cancer: Dealing with the Problem, Building on New Knowledge and Turning the Game Around. Cancers 2019, 11, 1141.
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