A5055973779- Neurofibromatosis and Schwannoma Cases
- Sarcoma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Meningioma and schwannoma management
- PI3K/AKT/mTOR signaling in cancer
- Chronic Myeloid Leukemia Treatments
- Thyroid Cancer Diagnosis and Treatment
- Glioma Diagnosis and Treatment
- Vascular Malformations Diagnosis and Treatment
- Soft tissue tumors and treatment
- Protein Degradation and Inhibitors
- Adrenal and Paraganglionic Tumors
- Lymphoma Diagnosis and Treatment
- Cancer-related gene regulation
- Bone Tumor Diagnosis and Treatments
- Neuroendocrine Tumor Research Advances
- Management of metastatic bone disease
- Spinal Hematomas and Complications
- Renal cell carcinoma treatment
- Quinazolinone synthesis and applications
- Cancer, Hypoxia, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Treatments and Mutations
- Multiple Myeloma Research and Treatments
- Soft tissue tumor case studies
National Cancer Institute
2016-2025
Center for Cancer Research
2016-2025
National Institutes of Health
2013-2025
Johns Hopkins University
2016-2025
Riley Hospital for Children
2025
Indiana University – Purdue University Indianapolis
2025
Cincinnati Children's Hospital Medical Center
2014-2023
University of California, San Francisco
2023
Boehringer Ingelheim (Germany)
2023
Boehringer Ingelheim (Austria)
2023
Effective medical therapies are lacking for the treatment of neurofibromatosis type 1–related plexiform neurofibromas, which characterized by elevated RAS–mitogen-activated protein kinase (MAPK) signaling.
No approved therapies exist for inoperable plexiform neurofibromas in patients with neurofibromatosis type 1.
Neurofibromatosis type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated controls numerous downstream effectors, but specific pathways mediating the effects in are unknown. We performed cross-species transcriptome analyses mouse human MPNSTs identified global negative feedback genes that regulate Ras/Raf/MEK/ERK signaling both...
Abstract Background Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many our previously published phase 1/2 trials (SPRINT, NCT01362803). At the data cutoff (DCO) of prior publications, 65% participants were still receiving treatment. This report presents up to 5 years additional safety efficacy from these studies. Methods manuscript includes 2, stratum study which included clinically...
People with neurofibromatosis 1 (NF1) have multiple benign neurofibromas and a 10% lifetime risk of developing malignant peripheral nerve sheath tumors (MPNSTs). Most MPNSTs develop from plexiform neurofibromas, so the burden may be factor for MPNST. We studied 13 NF1 patients 26 age- sex-matched controls (NF1 who did not MPNSTs) detailed clinical examinations whole-body MRI to characterize their body internal neurofibromas. Internal were identified in 22 (56%) 39 studied. All six under 30...
<b>Objective: </b> To longitudinally analyze changes in plexiform neurofibroma (PN) volume relation to age and body growth children young adults with neurofibromatosis type 1 inoperable, symptomatic, or progressive PNs, using a sensitive, automated method of volumetric MRI analysis. <b>Methods: We included patients 25 years younger PNs entered natural history study treatment trials who had over ≥16 months. <b>Results: studied 49 (median 8.3 years) 61 median evaluation period 34 months (range...
Medullary thyroid carcinoma (MTC) is a manifestation of multiple endocrine neoplasia type 2 (MEN2) syndromes caused by germline, activating mutations in the RET (REarranged during Transfection) proto-oncogene. Vandetanib, VEGF and EGF receptor inhibitor, blocks tyrosine kinase activity active adults with hereditary MTC.We conducted phase I/II trial vandetanib for children (5-12 years) adolescents (13-18 MTC to define recommended dose assess antitumor activity. The starting was 100 mg/m(2)...
Plexiform neurofibromas (PNs) are benign peripheral nerve sheath tumors that arise in one-third of individuals with neurofibromatosis type 1 (NF1). They may cause significant disfigurement, compression vital structures, neurologic dysfunction, and/or pain. Currently, the only effective management strategy is surgical resection. Converging evidence has demonstrated NF1 tumor suppressor protein, neurofibromin, negatively regulates activity mammalian Target Rapamycin pathway. We employed a...
Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these have become available. Due to differences in disease manifestations the natural history of NF-related tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria Solid Tumors] bidimensional/World Health Organization) limited applicability. No standardized NF exist. The goal...
To examine the natural growth dynamics of internal plexiform neurofibromas (PNs) in patients with neurofibromatosis 1 (NF1). Two hundred and one NF1 underwent whole body MRI (WBMRI). Tumour burden was estimated volumetrically. Non-parametric Spearman’s rho correlation coefficients were used to analyse relationship rate tumour volume age. Chi-squared Mann–Whitney U tests for analysing association occurrence sex or age group. Seventy-one 171 serial WBMRI exams had PNs (median follow up 2.2...
Introduction: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive soft tissue sarcomas in which complete surgical resection is the mainstay of therapy. However, recurrence rate high and few options remain for refractory or metastatic MPNST. This study examines outcomes adjuvant radiation therapy MPNST patients with without neurofibromatosis-1 (NF1) reviews literature on use Methods: A retrospective review 33 between 1990 2012 evaluated at NIH. All diagnoses were...
Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by bilateral vestibular schwannomas (VSs) resulting in deafness and brainstem compression. This study evaluated efficacy biomarkers of bevacizumab activity for NF2-associated progressive symptomatic VSs.Bevacizumab 7.5 mg/kg was administered every 3 weeks 46 weeks, followed 24 surveillance after treatment with the drug. The primary end point hearing response defined word recognition score (WRS). Secondary points...
Neurofibromatosis 1 (NF1) leads to the development of benign and malignant peripheral nerve sheath tumors (MPNST). MPNST have been described develop in preexisting plexiform neurofibromas (PN) a poor prognosis. Atypical (ANF) were recently as precursor lesions for MPNST, making early detection management ANF possible strategy prevent MPNST. We aimed clinically characterize identify approaches. analyzed clinical, imaging, pathology findings all patients with NF1 at 3 institutions. Sixty-three...
RAS is dysregulated in neurofibromatosis type 1 (NF1) related plexiform neurofibromas (PNs). The activity of tipifarnib, which blocks signaling by inhibiting its farnesylation, was tested children and young adults with NF1 progressive PNs.Patients aged 3-25 years NF1-related PNs imaging evidence tumor progression were randomized a double-blinded fashion to receive tipifarnib (200 mg/m(2) orally every 12 h) or placebo (phase A) crossed over the opposite treatment arm at time B). PN volumes...
PURPOSE Patients with neurofibromatosis type 1 (NF1) frequently develop plexiform neurofibromas (PNs), which can cause significant morbidity. We performed a phase II trial of the MAPK/ERK kinase inhibitor, mirdametinib (PD-0325901), in patients NF1 and inoperable PNs. The primary objective was response rate based on volumetric magnetic resonance imaging analysis. METHODS Inclusion criteria included age ≥ 16 years PN that either progressive or causing First-dose pharmacokinetics were...
Abstract Background Selumetinib was recently approved for the treatment of inoperable symptomatic plexiform neurofibromas (PNs) in children with neurofibromatosis type 1 (NF1). This parallel phase II study determined response rate to selumetinib NF1 PN without clinically significant morbidity. Methods Children and PNs, which were not yet causing morbidity but had potential cause symptoms, received at 25 mg/m2 orally twice daily (1 cycle = 28 days). Volumetric magnetic resonance imaging...