PI3K/AKT/mTOR inhibitors as potential extracellular matrix modulators for targeting EMT subtype gastric tumors.

Targeting the extracellular matrix (ECM) is considered as a promising strategy in cancer therapeutics. This study was designed to identify the potential ECM modulators for gastric cancer therapeutics. Exploration of the expression profiles of gastric tumors revealed the elevated expression of ECM genes in gastric tumor tissues compared to the adjacent normal tissues with increased expression in diffuse subtype gastric tumors and specifically in epithelial to mesenchymal transition (EMT) molecular subtype tumors. Consensus ECM gene set was derived from the expression profiles of gastric tumors. The correlative analysis was performed between the expression pattern of the ECM gene set and the drug sensitivity pattern of a panel of drugs across gastric cancer cell lines. Negative correlation between the expression of ECM genes and sensitivity of a number of drugs targeting PI3K/mTOR signaling, chromatin histone acetylation and ABL signaling was observed. These pathways are known for their role in cell-mediated adhesion, differentiation and epithelial to mesenchymal transition. The current results reveal the possibility of using PI3K/AKT/mTOR modulators for targeted gastric cancer therapy in patients with dysregulated ECM.