Skin of Color Representation in Clinical Trials: An Analysis of Clinicaltrials.gov From 2008-2022.

There is a plethora of dermatologic clinical trials; however, little is known regarding the representation of skin of color (SOC) populations. We evaluated the 15 most prevalent skin conditions in SOC patients and their representation in clinical trials over 14 years (2008-2022) to address the lack of research regarding dermatologic clinical trials and SOC inclusion. There have been 1,419 clinical trials conducted over the last 14 years regarding the 15 dermatologic conditions most commonly affecting SOC. Despite the prevalence of these conditions in SOC, Black/African American participation was greater than 50% in clinical trials for two conditions, keloids (77.9%) and seborrheic dermatitis (55.3%). Due to the disparities in inclusion, clinical trial data is difficult to extrapolate the results to SOC patients, limiting therapeutic options and potentially contributing to worse outcomes for such patients. Our study confirms that there is limited data available in clinical trials with respect to race, ethnicity, and FST. Further, it highlights how essential it is for SOC to be both adequately represented and reported in research regarding dermatologic skin conditions to ensure equality and equity in dermatologic care. J Drugs Dermatol. 2023;22(3) doi:10.36849/JDD.7087.

Executioner caspases restrict mitochondrial RNA-driven Type I IFN induction during chemotherapy-induced apoptosis.

During apoptosis, mitochondrial outer membrane permeabilization (MOMP) enables certain mitochondrial matrix macromolecules to escape into the cytosol. However, the fate of mitochondrial RNA (mtRNA) during apoptosis is unknown. Here, we demonstrate that MOMP results in the cytoplasmic release of mtRNA and that executioner caspases-3 and -7 (casp3/7) prevent cytoplasmic mtRNA from triggering inflammatory signaling. In the setting of genetic or pharmacological casp3/7 inhibition, apoptotic insults result in mtRNA activation of the MDA5/MAVS/IRF3 pathway to drive Type I interferon (IFN) signaling. This pathway is sufficient to activate tumor-intrinsic Type I IFN signaling in immunologically cold cancer models that lack an intact cGAS/STING signaling pathway, promote CD8+ T-cell-dependent anti-tumor immunity, and overcome anti-PD1 refractoriness in vivo. Thus, a key function of casp3/7 is to inhibit inflammation caused by the cytoplasmic release of mtRNA, and pharmacological modulation of this pathway increases the immunogenicity of chemotherapy-induced apoptosis.