Phospholipid ether-enriched domain (PLE) (PLE)

Phospholipid ether-enriched domain (PLE) is a specialized lipid microdomain that is significantly overexpressed on the surface of a wide variety of malignant cells compared to healthy cells (Source: Weichert et al., 2014). This domain is characterized by a high concentration of ether-linked phospholipids, which contribute to the unique structural and signaling properties of the cancer cell membrane (Source: Cellectar Biosciences). PLEs serve as a selective gateway for the entry of phospholipid drug conjugates (PDCs), which exploit the differential lipid composition of tumor membranes to achieve high intracellular concentrations of cytotoxic or imaging agents (Source: Journal of Nuclear Medicine, 2020). In oncology, targeting PLEs allows for a broad-spectrum approach, as these domains are found across numerous hematologic and solid tumor types, including multiple myeloma and glioblastoma (Source: Clinical Cancer Research, 2019). Drugs like iopofosine I-131 utilize this mechanism to deliver targeted radiation directly into the cytoplasm of cancer cells while sparing normal tissues that lack these enriched domains. This selective uptake is driven by the affinity of the phospholipid ether backbone for the PLE, followed by a flip-flop movement across the bilayer or endocytic internalization. Consequently, the PLE represents a unique non-protein therapeutic target that leverages the altered lipid metabolism inherent in oncogenesis.

Other names

Tumor cell plasma membrane phospholipid ether-enriched domainsCancer cell lipid raftsEther lipid-enriched microdomainsPLEs

Selective binding to and internalization through phospholipid ether-enriched domains (PLEs) overexpressed on cancer cell membranes, facilitating the delivery of therapeutic payloads (Source: Weichert et al., 2014).