Imlunestrant is an Oral, Brain-Penetrant Selective Estrogen Receptor Degrader with Potent Antitumor Activity in ESR1 Wildtype and Mutant Breast Cancer.

Targeting of the estrogen receptor (ER) by anti-estrogens is the standard-of-care for patients with ER+ HER2- advanced/metastatic breast cancer. While anti-estrogens that degrade ERα (fulvestrant) or block estrogen production (aromatase inhibitors) have improved patient outcomes, clinically important challenges remain related to drug administration, limited bioavailability, lack of brain exposure, and acquired resistance due to ESR1 mutations. These limitations indicate a need for more robust ER-targeted therapies.

HILPDA Regulates Lipid Metabolism, Lipid Droplet Abundance, and Response to Microenvironmental Stress in Solid Tumors.

Accumulation of lipid droplets has been observed in an increasing range of tumors. However, the molecular determinants of this phenotype and the impact of the tumor microenvironment on lipid droplet dynamics are not well defined. The hypoxia-inducible and lipid droplet associated protein HILPDA is known to regulate lipid storage and physiologic responses to feeding conditions in mice, and was recently shown to promote hypoxic lipid droplet formation through inhibition of the rate-limiting lipase adipose triglyceride lipase (ATGL).

Dynamic Heterogeneity of the Heart Valve Interstitial Cell Population in Mitral Valve Health and Disease.

The heart valve interstitial cell (VIC) population is dynamic and thought to mediate lay down and maintenance of the tri-laminar extracellular matrix (ECM) structure within the developing and mature valve throughout life. Disturbances in the contribution and distribution of valve ECM components are detrimental to biomechanical function and associated with disease. This pathological process is associated with activation of resident VICs that in the absence of disease reside as quiescent cells.

RNA-seq analysis to identify novel roles of scleraxis during embryonic mouse heart valve remodeling.

Heart valve disease affects up to 30% of the population and has been shown to have origins during embryonic development. Valvulogenesis begins with formation of endocardial cushions in the atrioventricular canal and outflow tract regions. Subsequently, endocardial cushions remodel, elongate and progressively form mature valve structures composed of a highly organized connective tissue that provides the necessary biomechanical function throughout life.