Author/Editor		Ocaña, Alberto; Vera-Badillo, Francisco Emilio; Al-Mubarak, Mustafa; Templeton, Arnoud J.; Corrales-Sanchez, Verónica; Diez-Gonzales, Laura; Cuenca-Lopez, Mária D.; Šeruga, Boštjan; Pandiella, Atanasio; Amir, Eitan
Title		Activation of the PI3K/mTOR/AKT pathway and survival in solid tumors
Type		članek
Vol. and No.		Letnik 9, št. 4
Publication year		2014
ISSN		1932-6203 - PloS one
Language		eng
Abstract		Aberrations in the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/AKT pathway are common in solid tumors. Numerous drugs have been developed to target different components of this pathway. However the prognostic value of these aberrations is unclear. METHODS: PubMed was searched for studies evaluating the association between activation of the PI3K/mTOR/AKT pathway (defined as PI3K mutation [PIK3CA], lack of phosphatase and tensin homolog [PTEN] expression by immunohistochemistry or western-blot or increased expression/activation of downstream components of the pathway by immunohistochemistry) with overall survival (OS) in solid tumors. Published data were extracted and computed into odds ratios (OR) for death at 5 years. Data were pooled using the Mantel-Haenszel random-effect model. RESULTS: Analysis included 17 studies. Activation of the PI3K/mTOR/AKT pathway was associated with significantly worse 5-year survival (OR:2.12, 95% confidence intervals 1.42-3.16, p<0.001). Loss of PTEN expression and increased expression/activation of downstream components were associated with worse survival. No association between PIK3CA mutations and survival was observed. Differences between methods for assessing activation of the PI3K/mTOR/AKT pathway were statistically significant (p%=%0.04). There was no difference in the effect of up-regulation of the pathway on survival between different cancer sites (p%=%0.13). CONCLUSION: Activation of the PI3K/AKT/mTOR pathway, especially if measured by loss of PTEN expression or increased expression/activation of downstream components is associated with poor survival. PIK3CA mutational status is not associated with adverse outcome, challenging its value as a biomarker of patient outcome or as a stratification factor for patients treated with agents acting on the PI3K/AKT/mTOR pathway.
Keywords		trdni tumorji imunohistokemija kemoterapija solid tumors immunohistochemistry chemotherapy