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PXD027187-1

PXD027187 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleATR inhibition enables complete tumour regression in ALK-driven NB mouse models
DescriptionHigh-risk neuroblastoma (NB) often involves amplification of the neural MYC (MYCN) oncogene as well as mutations in ALK. Currently, high-risk NB presents significant clinical challenges, and additional therapeutic options are needed. Oncogenes such as MYCN and ALK result in increased replication stress in cancer cells, offering one such therapeutically exploitable option. Here, we followed up on earlier phosphoproteomic analyses that identified ATR activity in ALK-driven NB cell lines. We tested several ATR inhibitors, identifying BAY 1895344 as the most potent inhibitor of NB cell growth and proliferation. Using RNA-Seq, proteomics and phosphoproteomics we characterized the response of NB cells and tumours to ATR inhibition, identifying key components of the DNA damage response (DDR) as well as ATRX, MYCN, E2F and DCK among other ATR targets in NB cells. ATR inhibition with BAY 1895344 also produced robust responses in mouse NB models. Remarkably, a 2 week protocol combining ATR and ALK inhibition led to complete regression of NB tumours in two independent NB genetically modified mouse tumour models. These results suggest that NB patients, particularly in high-risk groups with oncogene induced replication stress, may benefit from inhibition of ATR as therapeutic intervention.
HostingRepositoryPRIDE
AnnounceDate2021-11-02
AnnouncementXMLSubmission_2021-11-02_07:00:51.850.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterCarina Sihlbom
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-07-08 04:20:11ID requested
12021-11-02 07:00:52announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: ATR inhibitor, ALK, neuroblastoma, phosphorylation
Contact List
Carina Sihlbom
contact affiliationProteomics Core Facility, Sahlgrenska Academy, University of Gothenburg
contact emailcarina.sihlbom@gu.se
lab head
Carina Sihlbom
contact affiliationProteomics Core Facility / University of Gothenburg
contact emailcarina.sihlbom@gu.se
dataset submitter
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Dataset FTP location
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