PXD043034-2

PXD043034 is an original dataset announced via ProteomeXchange.

Title	KInome profiling of adult plexiform neurofibroma tissue before and after treatment with selumetinib: Phase 2 study of adults with inoperable plexiform neurofibroma
Description	The MEK inhibitor selumetinib induces objective responses in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). We conducted an open-label phase 2 study of selumetinib in 33 adults with PNs (NCT02407405). The objective response rate was 72.7% (24/33 patients). Median tumor volume decrease at best response was 23.6% at data cut-off with 19 patients continuing to receive study treatment. Acneiform rash was the most common adverse event (AE, 33/33 patients, 15 grade ≥2); acneiform rash and increases of ALT, AST, CPK, and lipase were the only grade 3/4 AEs to occur in more than 1 patient. Patients report improved pain levels and quality of life. Phosphorylation of ERK1/2 decreased significantly in paired biopsies (P≤0.0003) without compensatory phosphorylation of AKT1/2/3 (P =0.0697-0.9587). Selumetinib can induce sustained tumor volume decreases in adults with inoperable PNs and is well tolerated, while paired biopsies reveal novel pharmacodynamic insights. Kinase enrichment proteomic analysis was performed using patient pre-treatment/baseline and on-treatment specimens when sufficient material was obtained, with detectable on-target loss of binding of selumetinib targets MEK2 and MEK1 in treated samples.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:58:08.191.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Steven Angus
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-15 15:24:08	ID requested
1	2024-09-12 10:02:36	announced
⏵ 2	2024-10-22 06:58:08	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: NCT02407405, MEK1, MEK2,Neurofibromatosis type 1, kinase, clinical trial

Brigitte Widemann
contact affiliation	Pediatric Oncology Branch, National Cancer Institute, USA
contact email	widemanb@mail.nih.gov
lab head
Steven Angus
contact affiliation	Indiana University School of Medicine
contact email	sangus@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043034
     1. Label: PRIDE project
     2. Name: KInome profiling of adult plexiform neurofibroma tissue before and after treatment with selumetinib: Phase 2 study of adults with inoperable plexiform neurofibroma