A group of natural compounds (e.g., thapsigargin) that inhibit sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) and affect intracellular trafficking of the Notch receptor causing accumulation of unprocessed Notch1 in the ER/Golgi compartment have emerged as potential therapeutics in cancers associated with NOTCH1 mutations [235]. Here, NOTCH1 is linked to cancer.