*6.2.7. PI3 kinase/mammalian target of the rapamycin pathway inhibition*

Upregulation of the PI3k/Akt/mTOR pathway was associated with poor prognosis and could be implicated in the chemoresistance of gastric cancer [144].

Everolimus is an oral mTOR inhibitor demonstrated to have efficiency in both phase I and phase II studies, which have shown that everolimus monotherapy had a good response rate for advanced gastric cancer patients in the second-line setting [145, 146]. Unfortunately, the phase III GRANITE-1 trial investigating the everolimus monotherapy as a second-/third-line in patients with advanced gastric cancer did not show OS benefit, only the association of severe adverse reactions [147]. Therefore, the use of this agent in the treatment of gastric cancer needs further investigations.

Rapamycin has shown efficiency in preclinical studies and animal models against gastric cancer, increasing also the effectiveness of chemotherapeutic drugs [148]; nevertheless, its use in gastric cancer does not have enough support yet.
