title: Comparative drug screening in NUT midline carcinoma.
abstract: 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.
authors: Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research, University of Western Australia, Perth, Western Australia.
authors: A H
authors: AH
authors: Beesley
authors: Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research, University of Western Australia, Perth, Western Australia.
authors: A
authors: A
authors: Stirnweiss
authors: Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research, University of Western Australia, Perth, Western Australia.
authors: E
authors: E
authors: Ferrari
authors: Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research, University of Western Australia, Perth, Western Australia.
authors: R
authors: R
authors: Endersby
authors: Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research, University of Western Australia, Perth, Western Australia.
authors: M
authors: M
authors: Howlett
authors: ACRF Drug Discovery Centre for Childhood Cancer, Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, UNSW, Sydney, Australia.
authors: T W
authors: TW
authors: Failes
authors: ACRF Drug Discovery Centre for Childhood Cancer, Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, UNSW, Sydney, Australia.
authors: G M
authors: GM
authors: Arndt
authors: 1] Department of Pathology, Princess Margaret Hospital for Children, Perth, Western Australia [2] School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia.
authors: A K
authors: AK
authors: Charles
authors: School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia.
authors: C H
authors: CH
authors: Cole
authors: Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research, University of Western Australia, Perth, Western Australia.
authors: U R
authors: UR
authors: Kees
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D059003:Topoisomerase Inhibitors / Q000494:pharmacology; D050257:Tubulin Modulators / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D005419:Flavonoids; D015513:Oncogene Proteins; D010880:Piperidines; D059003:Topoisomerase Inhibitors; D050257:Tubulin Modulators; C077990:alvocidib; D014750:Vincristine; D004317:Doxorubicin