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.
Highlights
Most newly diagnosed lung cancer patients develop distant metastasis, which leads to poor survival, keeping lung cancer as the leading cause of cancer-related deaths worldwide
Higher expression levels of miR-328 and lower expression levels of PTEN were detected in cisplatin resistant compared with cisplatin sensitive non-small-cell lung cancer (NSCLC) patients [31]
The findings suggested a negative correlation between p-AktS473 and PTEN and poor survival for p-AktS473 positive/PTEN
Summary
Most newly diagnosed lung cancer patients develop distant metastasis, which leads to poor survival, keeping lung cancer as the leading cause of cancer-related deaths worldwide. Histological classification of lung cancer provides crucial information regarding treatment approach. Cancers 2019, 11, 1141 has been made in terms of precision medicine, in oncogene-addicted disease, chemotherapy still represents a crucial treatment option for the majority of lung cancer patients, albeit with usually a short-term survival benefit. The development of tyrosine kinase inhibitors (TKIs) and immunotherapy were major breakthroughs in lung cancer treatment providing an important survival benefit for subgroups of NSCLC. PI3K/mTOR/Akt is one of the most commonly genetically altered and deregulated oncogenic signaling pathways in cancer, including lung cancer and especially. Was discovered as a tumor suppressor gene and thereafter it was demonstrated that it acts as a master negative regulator of the PI3K/mTOR/Akt pathway. To date clinical trials with numerous agents targeting this pathway failed to demonstrate a solid clinical benefit
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