cblc137 has been researched along with Small-Cell-Lung-Carcinoma* in 2 studies
2 other study(ies) available for cblc137 and Small-Cell-Lung-Carcinoma
| Article | Year |
|---|---|
CBL0137 increases the targeting efficacy of Rovalpituzumab tesirine against tumour-initiating cells in small cell lung cancer.
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. Topics: Animals; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzodiazepinones; Carbazoles; Cell Proliferation; Drug Resistance, Neoplasm; Humans; Immunoconjugates; Lung Neoplasms; Mice; Mice, Inbred NOD; Mice, SCID; Prognosis; Small Cell Lung Carcinoma; Tumor Cells, Cultured; Xenograft Model Antitumor Assays | 2021 |
The FACT inhibitor CBL0137 Synergizes with Cisplatin in Small-Cell Lung Cancer by Increasing
Traditional treatments of small-cell lung cancer (SCLC) with cisplatin, a standard-of-care therapy, spare the tumor-initiating cells (TIC) that mediate drug resistance. Here we report a novel therapeutic strategy that preferentially targets TICs in SCLC, in which cisplatin is combined with CBL0137, an inhibitor of the histone chaperone facilitates chromatin transcription (FACT), which is highly expressed in TICs. Combination of cisplatin and CBL0137 killed patient-derived and murine SCLC cell lines synergistically. In response to CBL0137 alone, TICs were more sensitive than non-TICs, in part, because CBL0137 increased expression of the tumor suppressor Topics: Animals; Carbazoles; Cell Line, Tumor; Cell Self Renewal; Cell Survival; Cisplatin; Disease Models, Animal; DNA-Binding Proteins; Drug Synergism; High Mobility Group Proteins; Humans; Lung Neoplasms; Neoplastic Stem Cells; Receptor, Notch1; Signal Transduction; Small Cell Lung Carcinoma; Transcriptional Elongation Factors; Xenograft Model Antitumor Assays | 2018 |