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Topical bakuchiol for facial photoageing

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Bakuchiol is a plant‐derived phytochemical that is known to have retinoid‐like effects in vitro. Dhaliwal and colleagues report a randomized trial in which 44 healthy participants with a mean age of 47 years applied bakuchiol 0·5% cream or retinol 0·5% cream for 12 weeks. Bakuchiol and retinol both significantly decreased wrinkle surface area and hyperpigmentation, with no statistical difference between the compounds. The retinol users reported more facial skin scaling and stinging. The authors concluded that bakuchiol is comparable with retinol in its ability to improve photoageing and is better tolerated than retinol.

Dhaliwal S, Rybak I, Ellis S et al. Prospective, randomized, double‐blind assessment of topical bakuchiol and retinol for facial photoageing. Br J Dermatol 2019; 180: 289–296.

DOI: 10.1111/bjd.16918

Autophagy modulation in mitogen‐activated protein kinase kinase inhibitor‐resistant melanoma

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Patients with malignant melanoma often relapse following treatment with BRAF and/or mitogen‐activated protein kinase kinase (MEK) inhibitors due to development of drug resistance. The aim of the study by Verykiou and colleagues was to investigate regulation of CD271 (a stem cell marker that mediates tumour aggressiveness) during development of resistance by melanoma to the MEK inhibitor trametinib. They used patient‐derived tissue, in vitro culture of human cell lines and a zebrafish xenograft assay. Their results show that transient induction of CD271 is a critical regulator of the adaptive drug‐response phase of melanoma cells to trametinib. Genetic or chemical inhibition of CD271 prevents emergence of trametinib‐induced drug‐resistant melanoma subpopulations. Progression to trametinib resistance by melanoma subpopulations results in loss of CD271 expression and subsequent resistance to CD271 inhibitors, but not to the cytotoxic effects of autophagy modulation. Autophagy modulation through either inhibition of vacuolar protein sorting 34 or activation of cytotoxic autophagy with tetrahydrocannabinol effectively resensitizes drug‐resistant melanoma cells to trametinib in vitro and in vivo. The authors summarize the translational message of their study by concluding that combined autophagy modulation and MEK inhibition offers a novel personalized therapeutic strategy to overcome MEK inhibitor‐induced drug resistance for patients with BRAF‐mutant metastatic melanoma.