Report of the First International Symposium on NUT Carcinoma

Author:

French Christopher A.1ORCID,Cheng Michael L.2,Hanna Glenn J.2ORCID,DuBois Steven G.23,Chau Nicole G.4ORCID,Hann Christine L.5ORCID,Storck Simone6,Salgia Ravi7,Trucco Matteo8,Tseng Jennifer9,Stathis Anastasios1011,Piekarz Richard12ORCID,Lauer Ulrich M.13,Massard Christophe14ORCID,Bennett Kelly15,Coker Shodeinde16,Tontsch-Grunt Ulrike17ORCID,Sos Martin L.181920ORCID,Liao Sida21,Wu Catherine J.2ORCID,Polyak Kornelia2ORCID,Piha-Paul Sarina A.22,Shapiro Geoffrey I.2ORCID

Affiliation:

1. 1Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

2. 2Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

3. 3Boston Children's Hospital, Boston, Massachusetts.

4. 4British Columbia Cancer Agency Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

5. 5Johns Hopkins University School of Medicine, Baltimore, Maryland.

6. 6Swabian Children's Cancer Center, Department of Paediatrics and Adolescent Medicine, University Hospital Augsburg, Augsburg, Germany.

7. 7Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California.

8. 8Cleveland Clinic Children's, Cleveland, Ohio.

9. 9Orlando Health, Orlando, Florida.

10. 10Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland.

11. 11Faculty of Biomedical Sciences, Universita della Svizzera Italiana, Lugano, Switzerland.

12. 12Investigational Drug Branch, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis (DCTD), NCI, Bethesda, Maryland.

13. 13University Hospital Tübingen, Tübingen, Germany.

14. 14Gustave Roussy Cancer Campus-Molecular Radiotherapy and Therapeutic Innovation INSERM U1030, Faculty of Medicine Kremlin-Bicêtre and Paris-Saclay University, France.

15. 15AbbVie pharmaceuticals, Chicago, Illinois.

16. 16Bristol-Myers Squibb Company, Lawrenceville, New Jersey.

17. 17Boehringer Ingelheim, RCV, Vienna, Austria.

18. 18Institute of Pathology, Faculty of Medicine, University of Cologne and University Hospital Cologne, Cologne, Germany.

19. 19Department of Translational Genomics, University of Cologne, Cologne, Germany.

20. 20Center for Molecular Medicine Cologne, Faculty of Medicine and Faculty of Mathematics, University of Cologne, Cologne, Germany.

21. 21TScan Therapeutics, Waltham, Massachusetts.

22. 22Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Abstract

Abstract NUT carcinoma is a rare, aggressive cancer defined by rearrangements of the NUTM1 gene. No routinely effective treatments of NUT carcinoma exist, despite harboring a targetable oncoprotein, most commonly BRD4-NUT. The vast majority of cases are fatal. Poor awareness of the disease is a major obstacle to progress in the treatment of NUT carcinoma. While the incidence likely exceeds that of Ewing sarcoma, and BRD4-NUT heralded the bromodomain and extra-terminal domain (BET) inhibitor class of selective epigenetic modulators, NUT carcinoma is incorrectly perceived as “impossibly rare,” and therefore receives comparatively little private or governmental funding or prioritization by pharma. To raise awareness, propagate scientific knowledge, and initiate a consensus on standard and targeted treatment of NUT carcinoma, we held the First International Symposium on NUT Carcinoma on March 3, 2021. This virtual event had more than eighty attendees from the Americas, Europe, Asia, and Australia. Patients with NUT carcinoma and family members were represented and shared perspectives. Broadly, the four areas discussed by experts in the field included (1) the biology of NUT carcinoma; (2) standard approaches to the treatment of NUT carcinoma; (3) results of clinical trials using BET inhibitors; and (4) future directions, including novel BET bromodomain inhibitors, combinatorial approaches, and immunotherapy. It was concluded that standard chemotherapeutic approaches and first-generation BET bromodomain inhibitors, the latter complicated by a narrow therapeutic window, are only modestly effective in a minority of cases. Nonetheless, emerging second-generation targeted inhibitors, novel rational synergistic combinations, and the incorporation of immuno-oncology approaches hold promise to improve the prognosis of this disease.

Funder

NIH

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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