The Role of the JAK/STAT Pathway in the Pathogenesis and Treatment of Keloids: A Systematic Review

BACKGROUND Keloid scars impact 4.5% to 16% of the population, causing pain, pruritus, and disfigurement. They are a common, recurrent complication in dermatologic surgery, with limited treatment options. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway has been implicated in keloid formation, presenting a potential therapeutic target. OBJECTIVE To review the literature published on the role of the JAK/STAT pathway in keloid pathogenesis and treatment. MATERIALS AND METHODS A systematic review of clinical and experimental studies was conducted on October 21, 2024, using PubMed, Cochrane, Embase, MEDLINE, and Web of Science, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies examining JAK/STAT signaling in keloids were independently reviewed. RESULTS Of 109 retrieved articles, 23 met inclusion criteria (one clinical trial, 22 basic science studies). A trial of tofacitinib, a JAK1/3 inhibitor, showed reduced scar thickness, pruritus, and pain. Preclinical studies demonstrated that JAK2 and STAT3 inhibition reduced fibroblast proliferation and collagen deposition. Systemic side effects remain a concern. CONCLUSION The JAK/STAT pathway plays a key role in keloid fibrogenesis. Although JAK inhibitors show promise, further research is needed to confirm efficacy, refine specificity, and minimize systemic risks. Targeted JAK/STAT inhibition may improve keloid treatment in dermatologic surgery.