CBL0137 increases the targeting efficacy of Rovalpituzumab tesirine against tumour-initiating cells in small cell lung cancer

• DOI: 10.1038/s41416-020-01192-x
• Publication Date: 2020-12-01T02:03:26Z
• Authors: Daniel J. Lindner; Gary Wildey; Yvonne Parker; Afshin Dowlati; George R. Stark; Sarmishtha De
• Keywords: Benzodiazepinones; Immunoconjugates; Lung Neoplasms; Carbazoles; Apoptosis; Mice, SCID; Brief Communication; Antibodies, Monoclonal, Humanized; Prognosis; Small Cell Lung Carcinoma; Xenograft Model Antitumor Assays; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Drug Resistance, Neoplasm; Mice, Inbred NOD; Antineoplastic Combined Chemotherapy Protocols; Tumor Cells, Cultured; Animals; Humans; Cell Proliferation

Abstract Small cell lung cancer (SCLC) is characterised by high relapse rates. Tumour-initiating cells (TICs) are responsible for drug resistance and recurrence of cancer. Rovalpituzumab tesirine (Rova-T), a potent humanised antibody–drug conjugate, selectively targets delta-like protein 3, which highly expressed in SCLC TICs. The experimental CBL0137 (CBL) inhibits the histone chaperone FACT (facilitates chromatin transcription), required expression transcription factors that essential TIC maintenance. Rova-T CBL each target TICs as single agents. However, acquired or intrinsic to agents major problem Therefore, we investigated potential effect combining eradicate more effectively. Our preclinical studies report novel translatable therapeutic strategy dual targeting using combination with potentially increase survival patients.