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Brigitte C. Widemann, M.D.

Senior Investigator

Pediatric Oncology Branch


Building 10, Room 13C103
Bethesda MD, 20892


Research Topics

Anticancer drug discovery and development are moving towards a more rational and targeted approach. The application of new molecularly targeted agents to the treatment of childhood cancers and neurofibromatosis type 1 (NF1) is a research objective of the Pharmacology and Experimental Therapeutics Section (PETS). In addition to studying the pharmacology, pharmacokinetics, pharmacodynamics, and toxicities of these novel agents, it is also a goal of the PETS to evaluate novel clinical trial designs and trial endpoints, which may be more applicable for molecularly targeted agents. The clinical development of farnesyltransferase inhibitors (FTI), which inhibit the posttranslational farnesylation required for the activity of wild-type and mutant ras proteins for patients with NF1 and refractory leukemias serves as an example for this approach. Pharmacodynamic endpoints that assess the effect of FTI on the target enzyme and farnesylation of cellular proteins are important endpoints of these trials. The clinical development of antimetabolites, such as raltitrexed, and agents that modulate the effects of antimetabolites, such as the recombinant bacterial enzyme, carboxypeptidase-G2 (CPDG2), is another research focus. CPDG2 hydrolyzes methotrexate (MTX) to inactive metabolites. CPDG2 provides an alternative route of elimination for MTX for patients with high-dose MTX- induced renal dysfunction, and plasma MTX concentrations declined by >95 percent within minutes in all patients. The intrathecal administration of CPDG2 has also been successfully used as a rescue agent in patients who received accidental overdoses of intrathecal MTX. A new drug application for the use of CPDG2 in HDMTX-induced renal dysfunction will be filed based on our data.

We have collaborated with Robert Arceci, Johns Hopkins Oncology Center, Baltimore, MD; Frank Balis, T. Fojo, Elizabeth Fox, and Kathy Warren, NIH; Jean Belasco, Children's Hospital of Philadelphia; Susan Blaney, Baylor University; Stewart Goldman, Children's Memorial Hospital, Chicago, IL; David Gutmann, Washington University School of Medicine, St. Louis, MO; Douglas Hyder, Children's Hospital of Los Angeles; Regina Jakacki, Children's Hospital of Pittsburgh, PA; Mark Kieran, Dana-Farber Cancer Institute; Bruce Korf, Partners Center for Human Genetics, Boston, MA; Roger Packer, Children's Hospital National Medical Center; and Gregory Reaman, Children's Oncology Group.


Dr. Widemann is a senior investigator at the NCI Pediatric Oncology Branch (POB). After obtaining her M.D., from the University of Cologne, Germany, in 1986, Dr. Widemann received board certification in pediatrics in 1992 and was a hematology/oncology fellow at NCI POB from 1992 to 1995. She subsequently joined the Pharmacology and Experimental Therapeutics Section of POB and received tenure at NCI in 2009. Dr. Widemann's primary research interests are the development of targeted therapies for refractory childhood cancers and neurofibromatosis type 1-related tumors.

Selected Publications

  1. Widemann BC, Acosta MT, Ammoun S, Belzberg AJ, Bernards A, Blakeley J, Bretscher A, Cichowski K, Clapp DW, Dombi E, Evans GD, Ferner R, Fernandez-Valle C, Fisher MJ, Giovannini M, Gutmann DH, Hanemann CO, Hennigan R, Huson S, Ingram D, Kissil J, Korf BR, Legius E, Packer RJ, McClatchey AI, McCormick F, North K, Pehrsson M, Plotkin SR, Ramesh V, Ratner N, Schirmer S, Sherman L, Schorry E, Stevenson D, Stewart DR, Ullrich N, Bakker AC, Morrison H. CTF meeting 2012: Translation of the basic understanding of the biology and genetics of NF1, NF2, and schwannomatosis toward the development of effective therapies. Am J Med Genet A. 2014;164A(3):563-78.
  2. Widemann BC, Schwartz S, Jayaprakash N, Christensen R, Pui CH, Chauhan N, Daugherty C, King TR, Rush JE, Howard SC. Efficacy of glucarpidase (carboxypeptidase g2) in patients with acute kidney injury after high-dose methotrexate therapy. Pharmacotherapy. 2014;34(5):427-39.
  3. Widemann BC, Dombi E, Gillespie A, Wolters PL, Belasco J, Goldman S, Korf BR, Solomon J, Martin S, Salzer W, Fox E, Patronas N, Kieran MW, Perentesis JP, Reddy A, Wright JJ, Kim A, Steinberg SM, Balis FM. Phase 2 randomized, flexible crossover, double-blinded, placebo-controlled trial of the farnesyltransferase inhibitor tipifarnib in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas. Neuro Oncol. 2014;16(5):707-18.
  4. Widemann BC, Babovic-Vuksanovic D, Dombi E, Wolters PL, Goldman S, Martin S, Goodwin A, Goodspeed W, Kieran MW, Cohen B, Blaney SM, King A, Solomon J, Patronas N, Balis FM, Fox E, Steinberg SM, Packer RJ. Phase II trial of pirfenidone in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas. Pediatr Blood Cancer. 2014;61(9):1598-602.
  5. Dagalakis U, Lodish M, Dombi E, Sinaii N, Sabo J, Baldwin A, Steinberg SM, Stratakis CA, Widemann BC. Puberty and plexiform neurofibroma tumor growth in patients with neurofibromatosis type I. J Pediatr. 2014;164(3):620-4.
This page was last updated on May 20th, 2014