Altered pathways and their intersections within CTCL cells suggest multiple opportunities for single and combination therapeutic intervention. Mutations in the JAK/STAT pathway (JAK1, JAK2, JAK3, STAT3, and STAT5B) and the NF-κB pathway (NFKB2) have been previously described in CTCL. The pathways affected all ultimately inhibit both intrinsic and extrinsic apoptosis pathway activation. Inhibition of these pathways (eg, by the targeted agents assessed) overcomes resistance to apoptosis and drives malignant CTCL cell death. (Created with biorender.com.)