Venlafaxine reverses chemotherapy-induced alopecia through epithelial and dermal reprogramming at single-cell resolution

In parallel, dermal fibroblasts undergo inflammatory and stress-associated reprogramming accompanied by activation of IL-1, TNF, IL-6, and epithelial–mesenchymal transition signaling pathways. Chemotherapy also disrupts epithelial–mesenchymal communication through reduced expression of critical niche factors including FGF7, FGF10, and Slit2. Topical venlafaxine and its active metabolite desvenlafaxine preserved follicular architecture, suppressed apoptosis, and restored hair shaft elongation in both mouse CIA models and human hair follicle organ culture.

At single-cell resolution, venlafaxine reversed epithelial translational shutdown, reactivated differentiation and Wnt signaling programs, and attenuated fibroinflammatory remodeling, thereby restoring paracrine niche signaling and matrix cell proliferation. Collectively, these findings redefine CIA as a disorder characterized by coordinated epithelial functional arrest and dermal inflammatory remodeling and identify venlafaxine as a potential pharmacological strategy to mitigate chemotherapy-associated hair loss.