Journal
BRITISH JOURNAL OF CANCER
Volume 124, Issue 5, Pages 893-895Publisher
SPRINGERNATURE
DOI: 10.1038/s41416-020-01192-x
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Funding
- Concept Grant from the US Department of Defense (DoD) [LC170491]
- Case Comprehensive Cancer Center Athymic Animal and Xenograft Core
- NCI core grant [P30 CA043703-23]
- CDMRP [LC170491, 1100846] Funding Source: Federal RePORTER
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The study investigated the potential effect of combining Rova-T and CBL in small cell lung cancer to eradicate tumor-initiating cells more effectively, presenting a novel therapeutic strategy for increasing survival rates in SCLC patients.
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.
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