PI3K inhibitors such as PI-103, PI-828 and PX-866 may be developed as potential therapeutic agents for effective treatment of oral squamous cell carcinoma (OSCC) patients, associated with activated PI3K/Akt pathway.
Activation of phosphoinositide 3-kinase (PI3K)/pAKT(Ser473) frequently occurs in advanced HPV-positive oropharyngeal SCC and elevated pAKT(Ser473) levels represent a feature during progression of oropharyngeal SCC, indicating a critical role of the mammalian target of rapamycin (mTOR) complex.
Activity of the downstream PI3K effector protein kinase B (PKB) was higher in SqCas than in AdCas and was correlated with PIK3CA copy number (r = 0.75), suggesting that these copy number increases contribute to activation of PI3K signaling in SqCas of the lung.
After SCC transformation, the absence of G45 domain in DeltaG45 cells was associated with deficient extracellular signal-regulated kinase and phosphotidylinositol 3-kinase (PI3K) pathway activation, impaired invasion, deficient metalloproteinase activity, and absent tumorgenicity in vivo.
Computational analysis indicated that miR-296-3p targeted PTEN, which regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and PTEN is involved in the carcinogenesis of SCC. miR-296-3p directly regulated PTEN expression in head and neck cancer cells, with PTEN protein levels decreased in 4/19 the SCCs (21.0%), as compared with those in the IPs (76.4%).
Head and neck squamous cell carcinomas exhibit variable sensitivity to inhibitors of the PI3K/mTOR pathway, an important target of genomic alterations in this cancer type.
In silico screening of candidate therapeutic compounds using subtype-specific pathway components identified HDAC and PI3K inhibitors as potential treatments tailored to lung SqCC.
Knockdown of PLC-γ1 or PIKE blocked EGF-induced activation of class Ia PI3K and protein kinase C-ζ and phosphorylation of nucleolin in the nucleus as well as EGF-induced SCC cell proliferation.
Moreover, blocking the whole PI3K-AKT-mTOR pathway with the PI3K/mTOR dual inhibitor BEZ235 also showed efficacy in treating this subtype of lung SqCC.
mTORis do not significantly change the immunohistochemical expression of molecules upstream of the mTOR inhibition (pmTOR, PI3K, pAkt), in cutaneous SCC.
Our data suggest that the PI3K/AKT pathway is related to cell survival and proliferation in oral squamous cell carcinoma through its interaction with Bcl-2 family members.<br />.