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

Autor: Yvonne Parker, Gary Wildey, George R. Stark, Daniel J. Lindner, Sarmishtha De, Afshin Dowlati
Rok vydání: 2020
Předmět:
congenital
hereditary
and neonatal diseases and abnormalities
Cancer Research
Immunoconjugates
Lung Neoplasms
Tics
Carbazoles
Apoptosis
Mice
SCID
Drug resistance
Brief Communication
Antibodies
Monoclonal
Humanized
Small-cell lung cancer
Mice
03 medical and health sciences
Targeted therapies
0302 clinical medicine
Mice
Inbred NOD
Transcription (biology)
Antineoplastic Combined Chemotherapy Protocols
mental disorders
Tumor Cells
Cultured
medicine
Animals
Humans
Transcription factor
Cell Proliferation
Benzodiazepinones
Experimental drug
biology
business.industry
Rovalpituzumab tesirine
Prognosis
medicine.disease
Small Cell Lung Carcinoma
Xenograft Model Antitumor Assays
respiratory tract diseases
Chromatin
Histone
Oncology
Drug Resistance
Neoplasm
030220 oncology & carcinogenesis
Cancer research
biology.protein
business
Zdroj: British Journal of Cancer
ISSN: 1532-1827
0007-0920
Popis: 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 is highly expressed in SCLC TICs. The experimental drug CBL0137 (CBL) inhibits the histone chaperone FACT (facilitates chromatin transcription), which is required for the expression of transcription factors that are essential for TIC maintenance. Rova-T and CBL each target SCLC TICs as single agents. However, acquired or intrinsic resistance to single agents is a major problem in cancer. Therefore, we investigated the potential effect of combining Rova-T and CBL in SCLC to eradicate TICs more effectively. Our preclinical studies report a novel and highly translatable therapeutic strategy of dual targeting TICs using Rova-T in combination with CBL to potentially increase survival of SCLC patients.
Databáze: OpenAIRE
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