Seizure-related homolog 6 (SEZ6) is a transmembrane protein found on the cell surface of select neuronal lineage cells.1,2


SEZ6 is selectively expressed on neuroendocrine tumors, including small cell lung cancer (SCLC), central nervous system (CNS) tumors, and high-grade neuroendocrine carcinomas (NECs), with minimal normal cell expression.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

  1. Shimizu-Nishikawa K, et al. Cloning and characterization of seizure-related gene, SEZ-6. Biochem Biophys Res Commun. 1995;216(1):382-9.
  2. Gunnersen JM, et al. Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons. Neuron. 2007;56(4):621-39.
  3. 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.
  4. 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.