SEZ6
OVERVIEW
Seizure-related homolog 6 (SEZ6) is a transmembrane protein found on the cell surface of select neuronal lineage cells.1,2
IMPLICATIONS IN CANCER
SEZ6 is highly expressed on neuroendocrine neoplasms, including small cell lung cancer (SCLC), high-grade neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and central nervous system (CNS) tumors, and has limited expression in normal tissues outside of the blood-brain barrier.3 Accordingly, SEZ6 is a potential target for the development of novel antibody drug conjugates (ADC) carrying payloads designed to kill neuroendocrine tumor cells, thereby treating patients with such tumors.
Using a bioinformatic approach, RNA expression analysis and immunohistochemistry identified SEZ6 as a highly expressed surface marker in neuroendocrine tumors including SCLC, with limited expression in normal tissue.4
Related Research
- Shimizu-Nishikawa K, et al. Cloning and characterization of seizure-related gene, SEZ-6. Biochem Biophys Res Commun. 1995;216(1):382-9.
- Gunnersen JM, et al. Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons. Neuron. 2007;56(4):621-39.
- Kudoh S, et al. Significance of achaete-scute complex homologue 1 (ASCL1) in pulmonary neuroendocrine carcinomas; RNA sequence analyses using small cell lung cancer cells and Ascl1-induced pulmonary neuroendocrine carcinoma cells. Histochem Cell Biol. 2020;153(6):443-456.
- Wiedemeyer WR, et al. ABBV-011, A Novel, Calicheamicin-Based Antibody-Drug Conjugate, Targets SEZ6 to Eradicate Small Cell Lung Cancer Tumors. Mol Cancer Ther. 2022;21(6):986-998.
