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

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
DOI: 10.1038/s41416-020-01192-x Publication Date: 2020-12-01T02:03:26Z
ABSTRACT
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.
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