'Rac'-ing upstream to treat rheumatoid arthritis

Signal transduction pathways regulate the production and function of many cytokines implicated in immune-mediated diseases. Targeting these enzymes with small molecule inhibitors represents a fertile field for the treatment of rheumatoid arthritis. Recent successes with compounds that block upstream kinases suggest that proximal members of the signaling cascades, such as Rac and other Rho family enzymes, might have therapeutic potential. Balancing efficacy and toxicity, however, remains a significant challenge that will require careful evaluation.