دورية أكاديمية
Combined blockade of polo-like kinase and pan-RAF is effective against NRAS-mutant non-small cell lung cancer cells
| العنوان: | Combined blockade of polo-like kinase and pan-RAF is effective against NRAS-mutant non-small cell lung cancer cells |
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| المؤلفون: | Park, Siyeon, Kim, Tae Min, Cho, Sung-Yup, Kim, Soyeon, Oh, Yumi, Kim, Miso, Keam, Bhumsuk, Kim, Dong-Wan, Heo, Dae Seog |
| المساهمون: | 조성엽, 김동완, 허대석, Cho, Sung-Yup, Kim, Dong-Wan, Heo, Dae Seog |
| بيانات النشر: | Elsevier BV |
| سنة النشر: | 2020 |
| المجموعة: | Seoul National University: S-Space |
| مصطلحات موضوعية: | INHIBITION, GENOME, BRAF, PATIENT, PLK1, MEK, NRAS-mutant lung cancer, High-throughput screening, Pan-RAF inhibitor, PLK1 inhibitor |
| الوصف: | NRAS mutation is rarely observed in non-small cell lung cancer (NSCLC) patients, and there are no approved treatments for NRAS-mutant NSCLC. Here, we evaluated the effect of pan-RAF inhibitors on human NRAS-mutant NSCLC cell lines and performed high-throughput screening using human kinome small interfering (si) RNA or CRISPR/Cas9 libraries to identify new targets for combination NSCLC treatment. Our results indicate that human NRAS-mutant NSCLC cells are moderately sensitive to pan-RAF inhibitors. High-throughput kinome screenings further showed that G2/M arrest, particularly following knockdown of polo-like kinase 1 (PLK1), can inhibit the growth of human NRAS-mutant NSCLC cells and those treated with the type II pan-RAF inhibitor LXH254. In addition, treatment with volasertib plus LXH254, resulting in dual blockade of PLK1 and pan-RAF, was found to be more effective than LXH254 monotherapy for inhibiting long-term cell viability, suggesting that this combination therapeutic strategy may lead to promising results in the clinic. ; N ; 1 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0304-3835 |
| العلاقة: | Cancer Letters, Vol.495, pp.135-144; 118788; https://hdl.handle.net/10371/171807Test; 000590212800003; 2-s2.0-85091652639 |
| DOI: | 10.1016/j.canlet.2020.09.018 |
| الإتاحة: | https://doi.org/10.1016/j.canlet.2020.09.018Test https://hdl.handle.net/10371/171807Test |
| رقم الانضمام: | edsbas.D362F79B |
| قاعدة البيانات: | BASE |
| تدمد: | 03043835 |
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| DOI: | 10.1016/j.canlet.2020.09.018 |