Systematic comparison of in vitro, preclinical, and clinical investigations has not only demonstrated the concordance of the anti-inflammatory and antiproliferative effects exerted upon the PI3K/AKT/mTOR signaling axis, but has also elucidated the fundamental mechanisms underlying the disruption of autocrine and paracrine circuits between RA-FLSs and immune system cells. Here, MTOR is linked to rheumatoid arthritis.