In the present study, we characterized the antitumor profile of PI3K inhibitors, in particular ZSTK474 which we developed, against sarcomas in preclinical models by exploiting a panel of sarcoma cell lines derived from various origin; in this respect, effects on tumor growth, PI3K-downstream signaling pathway and apoptosis induction in vitro and in vivo were assessed. This evidence concerns the gene PIK3CA and neoplasm.