The Ca2+ stored in the cellular endoplasmic reticulum (ER) plays a crucial role in protein folding and lipid transfer, and its impairment leads to cellular ER stress. When chronic cellular ER stress occurs in the liver, it triggers the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Previous reports found that NACHT and WD repeat domain containing 1 (NWD1) localized in the ER and mitochondria in neural stem/progenitor cells, but the significance of NWD1 outside the brain is not well known.

Neuroblastoma, an aggressive malignancy originating from neural crest cells, accounts for 15% of cancer-related deaths in children. Treatment strategies include systemic chemotherapy, radiation or immunotherapy with anti-GD2 antibodies, all with severe side effects and long-term toxicity. Retinoic acid (RA) has been shown to promote neuroblastoma growth inhibition while suppressing MYCN oncogene expression. However, its effect is reversible, and tumor regrowth may occur.

Additional early-stage research and drug discovery news in brief, from: Atyr Pharma, Lixte Biotechnology, Oligomerix, Promis Neurosciences.

Onkure Therapeutics Inc. has described phosphatidylinositol 3-kinase α (PI3Kα) (H1047R mutant) inhibitors reported to be useful for the treatment of cancer, congenital lipomatous overgrowth, vascular malformations, epidermal naevi and skeletal abnormalities, scoliosis and PIK3CA related overgrowth spectrum (PROS), among others.