HDAC8-mediated inhibition of EP300 drives a transcriptional state that increases melanoma brain metastasis.

Melanomas can adopt multiple transcriptional states. Little is known about the epigenetic drivers of these cell states, limiting our ability to regulate melanoma heterogeneity. Here, we identify stress-induced HDAC8 activity as driving melanoma brain metastasis development.

HDAC11 activity contributes to MEK inhibitor escape in uveal melanoma.

We previously demonstrated that pan-HDAC inhibitors could limit escape from MEK inhibitor (MEKi) therapy in uveal melanoma (UM) through suppression of AKT and YAP/TAZ signaling. Here, we focused on the role of specific HDACs in therapy adaptation. Class 2 UM displayed higher expression of HDACs 1, 2, and 3 than Class 1, whereas HDACs 6, 8, and 11 were uniformly expressed.

Ironing-Out the Details: New Strategies for Combining Ferroptosis Inhibitors with Immunotherapy in Melanoma.

Escape from ferroptosis is an important determinant of metastasis and immune evasion in melanoma. In a new article of the Journal of Investigative Dermatology, Wang et al. (2021) identify the CAMKK2‒adenosine monophosphate-activated protein kinase‒NRF2 signaling axis as a negative regulator of ferroptosis and showed that inhibiting CAMKK2 increases the efficacy of anti-PD-1 therapy.

Protect Our Kids: a novel program bringing hemorrhage control to schools.

Background: Following the shooting at Sandy Hook Elementary School, the Hartford Consensus produced the Stop the Bleed program to train bystanders in hemorrhage control. In our region, the police bureau delivers critical incident training to public schools, offering instruction in responding to violent or dangerous situations. Until now, widespread training in hemorrhage control has been lacking.

Noncanonical EphA2 Signaling Is a Driver of Tumor-Endothelial Cell Interactions and Metastatic Dissemination in BRAF Inhibitor‒Resistant Melanoma.

Acquired BRAF/MAPK/extracellular signal‒regulated kinase inhibitor resistance in melanoma results in a new transcriptional state associated with an increased risk of metastasis. In this study, we identified noncanonical ephrin receptor (Eph) EphA2 signaling as a driver of the resistance-associated metastatic state. We used mass spectrometry‒based proteomic and phenotypic assays to demonstrate that the expression of active noncanonical EphA2-S897E in melanoma cells led to a mesenchymal-to-amoeboid transition driven by Cdc42 activation.