JAK-STAT pathway inhibitors in dermatology

Abstract

The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different JAK-STAT signaling patterns have potential indications for various medical conditions. The main dermatological targets of JAK-STAT pathway inhibitors are inflammatory or autoimmune diseases such as psoriasis, vitiligo, atopic dermatitis and alopecia areata; however, several dermatoses are under investigation to expand this list of indications. As JAK-STAT pathway inhibitors should gradually occupy a relevant space in dermatological prescriptions, this review presents the main available drugs, their immunological effects, and their pharmacological characteristics, related to clinical efficacy and safety, aiming to validate the best dermatological practice.

Keywords: Alopecia areata; Atopic dermatitis; Janus Kinase Inhibitors; Psoriasis; Treatment; Vitiligo.

Figure 1

Schematic representation of the (canonical) JAK-STAT signaling pathway. (A) Several cytokines and growth factors present in the extracellular environment depend on transmembrane receptors to initiate the process of cell signaling and nuclear transcription of the genes associated with each pathway. (B) Cytokine coupling with the extracellular domain of the transmembrane receptor leads to a change in its conformation and phosphorylation of JAK dimers, located in the intracellular domain of the receptor, that transphosphorylate their terminal tyrosine residues. This process induces the dimerization and phosphorylation of inactive STAT units that migrate to the nucleus and mediate the transcription of genes related to the specific cytokine pathway. (C) Inhibitors of the JAK-STAT (JAKi) signaling pathway prevent JAK phosphorylation by disrupting cytokine or growth factor nuclear signaling. Source: the authors

Figure 2

Diagram representing the main JAKi that show favorable results in clinical studies for inflammatory and autoimmune dermatoses. AA, Alopecia areata; AD, Atopic dermatitis; DM, Dermatomyositis; PSO, Psoriasis; VITI, Vitiligo; HS, Hidradenitis suppurativa; GVHD, Graft-versus-host disease; Abro, Abrocitinib; Upa, Upadacitinib; Bari, Baricitinib; TDelgo, Topical Delgocitinib; Tofa, Tofacitinib; TRuxo, Topical Ruxolitinib; Ruxo, Ruxolitinib; Ritle, Ritlecitinib; Deucra, Deucravacitinib; Solci, Solcitinib; Itaci, Itacitinib; Deuruxo, Deuruxolitinib