Anti-Acne Agents Attenuate FGFR2 Signal Transduction in Acne

The document from 2009 discusses the hypothesis that anti-acne agents work by reducing the signaling of fibroblast growth factor receptor-2 (FGFR2), which is believed to play a significant role in the development of acne. It suggests that increased FGFR2 signaling is involved in acne pathogenesis, particularly in conditions like Apert syndrome and unilateral acneiform nevus, which are associated with FGFR2 mutations. The article outlines how various anti-acne drugs may inhibit FGFR2 signaling: anti-androgens suppress FGF-ligand expression; benzoyl peroxide leads to FGFR2 downregulation through lysosomal receptor degradation; azelaic acid blocks mitochondrial ATP formation, which is necessary for receptor tyrosine kinase phosphorylation; tetracyclines inhibit the expression and activity of FGFR2b downstream matrix metalloproteinases; retinoids reduce FGFR2 signaling at multiple regulatory points in the signal transduction cascade that are crucial for cell cycle control, cell proliferation, differentiation, and lipogenesis; and erythromycin, as a P-450 inhibitor, may affect FGFR2 signaling by inhibiting retinoid catabolism. These mechanisms highlight the potential role of FGFR2 signaling in acne and support the therapeutic targeting of this pathway by anti-acne medications.