Topical
retinoids are the cornerstone of current
acne management due to their actions on multiple facets of
acne pathophysiology.
Retinoids are a family of compounds that structurally and functionally resemble
vitamin A, an essential nutrient with a key role in cellular growth and differentiation. In the skin,
retinoids exert their effects by binding
retinoic acid receptors (RARs) in the cell nucleus with subsequent regulation of gene transcription. There are three subtypes of RARs, and the topical
retinoids currently approved for
acne have differing receptor binding profiles which may translate to clinical differences, since the specific RAR subtypes activated dictate the biological response of target cells. The activity of a
retinoid depends on cellular transport, receptor-binding pattern and affinity, and the genes activated. This review discusses physiologic pathways in skin that are affected by topical
retinoids during
acne therapy, with a focus on new data from
trifarotene, a
retinoid which is highly selective for the
RAR-γ receptor. Recently, bioinformatic data comparing gene expression in
acne lesions treated with
trifarotene versus spontaneously resolving
acne lesions showed that
trifarotene significantly modulates 67 genes that do not appear in the spontaneously resolving lesion. These genes are involved in cellular migration, activation of adaptive immunity,
inflammation, and matrix reorganization. Expression of these
trifarotene-regulated genes
after treatment and in an active lesion occurred in opposite directions, providing clues to the molecular and genetic response to
trifarotene in resolving
acne. J Drugs Dermatol. 2022;21(7):734-740. doi:10.36849/JDD.6890.