New Frontiers in Dermatology: Defining the JAK-STAT Pathway

On July’s episode Derm Discussions, Brett King, MD, PhD, of Yale School of Medicine, offered perspectives on the emerging role of Janus Kinase (JAK) inhibitors in dermatology.

Before diving into the class’s potential across various dermatologic disease states, he provided an overview of the JAK-STAT pathway, noting its relationship to cytokines.

“At least 50 [of the known 200 cytokines] signal through the JAK-STAT pathway,” he said. “Think of signaling as a relay race, in which the extracellular cytokine binds to its unique receptor on the cell surface and passes the baton to an intracellular JAK protein — which passes the baton to a STAT protein, which goes to the nucleus and makes disease happen.”

Blocking a JAK protein would disrupt the signaling leading to disease.

These proteins include JAK 1, JAK 2, JAK 3, and tyranise kinase 2 (TYK 2). Since the enzymes are small molecules, JAK inhibitors are thus able to be administered either orally or topically.

King further noted that JAK inhibitors operate on a different level of targeted therapy form biologics.

“These agents are not biologics,” he stressed. “We are not targeting a cytokine, but we are also not knocking down all T-cells like with cyclosporine. These are sort-of non-targeted targeted therapies.”

Listen to the full podcast episode below: