• Junne Kamihara, Kayla V Hamilton, Jessica A Pollard, Catherine M Clinton, Jill A Madden, Jasmine Lin, Alma Imamovic, Catherine B Wall, Ari J Wassner, Brent R Weil, Matthew M Heeney, Sara O Vargas, William G Kaelin, Katherine A Janeway, Rodolfo F Perini, Naseem J Zojwalla, Stephan D Voss, and Steven G DuBois.
• From the Departments of Pediatric Oncology (J.K., K.V.H., J.A.P., C.M.C., A.I., C.B.W., K.A.J., S.G.D.) and Medical Oncology (W.G.K.), Dana-Farber Cancer Institute, Harvard Medical School, the Divisions of Hematology and Oncology (J.K., J.A.P., M.M.H., K.A.J., S.G.D.) and Endocrinology (A.J.W.) and the Departments of Surgery (B.R.W.), Pathology (S.O.V.), and Radiology (S.D.V.), Boston Children's Hospital, Harvard Medical School, and the Manton Center for Orphan Disease Research and the Division of Genetics and Genomics, Boston Children's Hospital (J.A.M., J.L.) - all in Boston; Howard Hughes Medical Institute, Chevy Chase, MD (W.G.K.); and Merck, Kenilworth, NJ (R.F.P., N.J.Z.).
• N. Engl. J. Med. 2021 Nov 25; 385 (22): 205920652059-2065.

AbstractThe integration of genomic testing into clinical care enables the use of individualized approaches to the management of rare diseases. We describe the use of belzutifan, a potent and selective small-molecule inhibitor of the protein hypoxia-inducible factor 2α (HIF2α), in a patient with polycythemia and multiple paragangliomas (the Pacak-Zhuang syndrome). The syndrome was caused in this patient by somatic mosaicism for an activating mutation in EPAS1. Treatment with belzutifan led to a rapid and sustained tumor response along with resolution of hypertension, headaches, and long-standing polycythemia. This case shows the application of a targeted therapy for the treatment of a patient with a rare tumor-predisposition syndrome. (Funded by the Morin Family Fund for Pediatric Cancer and Alex's Lemonade Stand Foundation.).Copyright © 2021 Massachusetts Medical Society.

33 keywords...

hide…