Protein delta homolog 1 (DLK1) (DLK1)

Protein delta homolog 1 (DLK1), also widely known as Pref-1, is a non-canonical Notch ligand and a transmembrane glycoprotein that plays a critical role in maintaining the undifferentiated state of various progenitor cells during embryonic development. It is part of the epidermal growth factor-like family and acts as a key inhibitor of adipocyte differentiation, while also regulating neurogenesis, myogenesis, and hematopoiesis. While its expression is restricted to a few adult tissues, such as the pituitary and adrenal glands, DLK1 is frequently overexpressed in several aggressive malignancies, including neuroblastoma, small cell lung cancer, and hepatocellular carcinoma. In these contexts, DLK1 functions as a marker for cancer stem cells, driving tumor proliferation and conferring resistance to standard chemotherapies. Its tumor-selective cell surface expression makes it an attractive target for therapeutic interventions such as antibody-drug conjugates (ADCs), which utilize DLK1 to deliver potent cytotoxic agents directly to malignant cells. Current clinical candidates like ADCT-701 and CBA-1205 are being investigated to exploit this specificity for the treatment of refractory neuroendocrine and solid tumors.

Other names

Delta-like 1 homologPreadipocyte factor 1Pref-1Fetal antigen 1FA1pG2ZOGDelta-like homologue 1Delta1

Targeting via antibody-drug conjugates (ADCs) to deliver cytotoxic payloads (e.g., PBD dimers); antibody-dependent cellular cytotoxicity (ADCC) enhancement; ligand-receptor interaction blockade to inhibit cancer stem cell maintenance and promote differentiation.