1. DLL3: an emerging target in small cell lung cancer
- Author
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Giffin Michael John, Marie-Anne Damiette Smit, Kai He, Dwight H. Owen, David P. Carbone, and Julie M. Bailis
- Subjects
0301 basic medicine ,Cancer Research ,Immunoconjugates ,Lung Neoplasms ,medicine.medical_treatment ,Review ,Neuroendocrine tumors ,Targeted therapy ,0302 clinical medicine ,Molecular Targeted Therapy ,Benzodiazepinones ,Hematology ,Bispecific T cell engager (BiTE®) antibody construct ,Intracellular Signaling Peptides and Proteins ,Small cell lung cancer (SCLC) ,lcsh:Diseases of the blood and blood-forming organs ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.anatomical_structure ,Neuroendocrine ,Oncology ,030220 oncology & carcinogenesis ,Chimeric Antigen Receptor T-Cell Therapy ,medicine.medical_specialty ,T cell ,Antineoplastic Agents ,Antibodies, Monoclonal, Humanized ,lcsh:RC254-282 ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Humans ,Molecular Biology ,Chemotherapy ,business.industry ,lcsh:RC633-647.5 ,Rovalpituzumab tesirine ,Membrane Proteins ,Antibody-drug conjugate (ADC) ,medicine.disease ,Small Cell Lung Carcinoma ,respiratory tract diseases ,Radiation therapy ,030104 developmental biology ,Immuno-oncology therapy ,Cancer research ,business ,Chimeric antigen receptor (CAR) T cell therapy ,Delta-like ligand 3 (DLL3) - Abstract
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers. Despite high rates of response to first-line chemotherapy and radiotherapy, patients with extensive-stage disease eventually relapse, and very few patients survive more than 5 years from diagnosis. Treatment options for recurrent or refractory disease are limited, and the treatments that do exist are associated with significant treatment-related toxicities. Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand that is highly expressed in SCLC and other neuroendocrine tumors but minimally expressed in normal tissues. It is therefore being explored as a potential therapeutic target in SCLC. Here, we review the preclinical and clinical evidence for targeting DLL3 in SCLC and discuss several DLL3-specific therapies being developed for the treatment of SCLC: the antibody-drug conjugate rovalpituzumab tesirine, the bispecific T cell engager immuno-oncology therapy AMG 757, and the chimeric antigen receptor T cell therapy AMG 119.
- Published
- 2019