Comparative drug screening in NUT midline carcinoma
| Autor: | E. Ferrari, Meegan Howlett, Anja Stirnweiss, Raelene Endersby, Adrian Charles, Catherine H. Cole, Timothy W. Failes, Ursula R. Kees, Alex H. Beesley, Greg M. Arndt |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Vincristine BRD4 Topoisomerase Inhibitors medicine.drug_class Mice Nude Antineoplastic Agents CDK9 Biology vincristine Mice midline carcinoma Piperidines In vivo Cell Line Tumor bromodomain medicine Animals Humans Anthracyclines Doxorubicin Vorinostat Etoposide Flavonoids Oncogene Proteins NUT NUT midline carcinoma Mice Inbred BALB C therapy medicine.disease Xenograft Model Antitumor Assays Tubulin Modulators flavopiridol Oncology Head and Neck Neoplasms Immunology Carcinoma Squamous Cell Cancer research Female Drug Screening Assays Antitumor Translational Therapeutics Topoisomerase inhibitor medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background: The NUT midline carcinoma (NMC) is a rare but fatal cancer for which systematic testing of therapy options has never been performed. Methods: On the basis of disease biology, we compared the efficacy of the CDK9 inhibitor flavopiridol (FP) with a panel of anticancer agents in NMC cell lines and mouse xenografts. Results: In vitro anthracyclines, topoisomerase inhibitors, and microtubule poisons were among the most cytotoxic drug classes for NMC cells, while efficacy of the bromodomain inhibitor JQ1 varied considerably between lines carrying different BRD4 (bromodomain-containing protein 4)–NUT (nuclear protein in testis) translocations. Efficacy of FP was comparable to vincristine and doxorubicin, drugs that have been previously used in NMC patients. All three compounds showed significantly better activity than etoposide and vorinostat, agents that have also been used in NMC patients. Statins and antimetabolites demonstrated intermediate single-agent efficacy. In vivo, vincristine significantly inhibited tumour growth in two different NMC xenografts. Flavopiridol in vivo was significantly effective in one of the two NMC xenograft lines, demonstrating the biological heterogeneity of this disease. Conclusions: These results demonstrate that FP may be of benefit to a subset of patients with NMC, and warrant a continued emphasis on microtubule inhibitors, anthracyclines, and topoisomerase inhibitors as effective drug classes in this disease. |
| Databáze: | OpenAIRE |
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