LEE011 and ruxolitinib: a synergistic drug combination for natural killer/T-cell lymphoma (NKTCL)
| Autor: | Junli Yan, Dean Nizetic, Yan Ting Hee, Wee Joo Chng |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug Ruxolitinib ruxolitinib media_common.quotation_subject drug combination lymphoma Growth inhibitory 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cyclin D1 Medicine LEE011 media_common business.industry EZH2 NKTCL medicine.disease Natural killer T cell Lymphoma 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Cancer research Growth inhibition business Research Paper medicine.drug |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.25835 |
| Popis: | Natural killer/T-cell lymphoma (NKTCL) is an aggressive non-Hodgkin lymphoma that has been facing limited success with conventional treatments, urging for the discovery of alternative strategies. Recent studies including ours have revealed that EZH2 and JAK-STAT signalling pathways are key contributors to NKTCL pathogenesis. In particular, we found that EZH2 is overexpressed and directly transcriptionally activates the CCND1 gene to confer growth advantage. CCND1 codes for cyclin D1, which complexes with CDK4/6 to promote G1 to S phase transition. Therefore in this study we investigated whether inhibiting both JAK1/2 and CDK4/6, using LEE011 and ruxolitinib respectively is effective in NKTL. We first demonstrate that separate LEE011 and ruxolitinib treatment is sufficient to cause growth inhibition of NKTCL cells. More importantly, we found that there is synergistic growth inhibitory effects on NKTCL cells with combination treatment of LEE011 and ruxolitinib. The results obtained shows that the targeting of both CDK4/6 and JAK1/2 are promising to develop better treatment alternatives for NKTCL. |
| Databáze: | OpenAIRE |
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