Molecular Pathology of Lung Cancer by unknow

Author:unknow
Language: eng
Format: epub, pdf
Publisher: Springer New York, New York, NY

PI3K/AKT/mTOR

The PI3K/AKT/mTOR pathway is involved in early stages of lung cancer development. PI3K are lipid kinases grouped into three classes (I–III) depending on their sequence homology and substrates. PIK3CA amplification (12–17%) and mutations (2%) have been found in NSCLC [45–47]. There are numerous drugs that interfere with this pathway at multiple levels. mTOR inhibitors (e.g., temsirolimus, everolimus) showed some promising results in KRAS-mutated cell lines [48]. Preclinical data also suggest that coexisting KRAS and PIK3CA mutations may be associated with resistance to PI3K/AKT/mTOR inhibitors [49]. PI3K inhibitors have shown efficacy in ­preclinical studies and are currently being tested in early phase clinical trials [49–51]. Drugs that inhibit PI3K/AKT/mTOR pathway may be active even in the absence of PIK3CA mutations, possible because of alterations in other genes in this pathway such as AKT activation and PTEN loss.

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