Low-density lipoprotein receptor (LDLR) (LDLR)

The Low-density lipoprotein receptor (LDLR) is a cell-surface glycoprotein that mediates the endocytosis of cholesterol-rich low-density lipoprotein particles, playing a central role in systemic cholesterol homeostasis (UniProt: P01130). In oncology, LDLR and its related family members, such as Low-density lipoprotein receptor-related protein 1 (LRP1), are frequently overexpressed by tumor cells to support the high lipid requirements of rapid cell division and membrane synthesis (PMID: 31434055). This overexpression, particularly in cancers like glioblastoma and pancreatic adenocarcinoma, makes these receptors attractive targets for receptor-mediated drug delivery. Therapeutic strategies include the use of peptide-drug conjugates (e.g., Angiopep-2) and nanoparticles designed to bind these receptors and trigger internalization of cytotoxic payloads. While cardiovascular therapies like PCSK9 inhibitors (e.g., Evolocumab) and statins modulate LDLR levels to manage hypercholesterolemia, oncology applications focus on the receptor as a gateway for intracellular delivery. Key challenges include the high physiological expression of LDLR in the liver, which can lead to significant off-target uptake and potential hepatotoxicity (PMID: 28636045).

Other names

LDL receptorApolipoprotein B/E receptorLRP1Low-density lipoprotein receptor-related protein 1CD91LRP2Megalin

PCSK9 inhibition to increase receptor recycling; HMG-CoA reductase inhibition to induce receptor expression; Receptor-mediated endocytosis of ligand-drug conjugates.