溴尿嘧啶
BRD4
癌症
医学
表观遗传学
癌症研究
作者
Christopher A. French,Michael L Cheng,Glenn J. Hanna,Steven G DuBois,Nicole G Chau,Christine L. Hann,Simone Storck,Ravi Salgia,Matteo Trucco,Jennifer Tseng,Anastasios Stathis,Richard Piekarz,Ulrich M Lauer,Christophe Massard,Kelly Bennett,Shodeinde Coker,Ulrike Tontsch-Grunt,Martin L. Sos,Sida Liao,Catherine J. Wu,Kornelia Polyak,Sarina A Piha-Paul,Geoffrey I. Shapiro
标识
DOI:10.1158/1078-0432.ccr-22-0591
摘要
NUT carcinoma (NC) is a rare, aggressive cancer defined by rearrangements of the NUTM1 gene. No routinely effective treatments of NC 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 NC. 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, NC 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 NC, we held the First International Symposium on NUT Carcinoma on March 3rd, 2021. This virtual event had over eighty attendees from the Americas, Europe, Asia, and Australia. NC patient and family members were represented and shared perspectives. Broadly, the four areas discussed by experts in the field included (1) the biology of NC; (2) standard approaches to the treatment of NC; (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.