PXD021865

PXD021865 is an original dataset announced via ProteomeXchange.

Title	Kinome profiling in HER2+ breast cancer patients in response to 7 days of HER2-targeting
Description	Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial (ClinicalTrials.gov Identifier: NCT01875666, LCCC1214) designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 transcription factor expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. Patient samples from this trial, when sufficient material was available, were also subjected to kinase enrichment using multiplexed kinase inhibitor bead affinity chromatography and LC-MS/MS. Strongly responsive transcriptional responses observed in a subset of patients corresponded to decreased binding of CDK1 and DDR1 by our proteomic approach. Taken together, our results highlight the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy.
HostingRepository	PRIDE
AnnounceDate	2021-04-09
AnnouncementXML	Submission_2021-04-08_23:05:15.760.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	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-06 23:02:49	ID requested
⏵ 1	2021-04-08 23:05:16	announced

Dataset with its publication pending

submitter keyword: ERBB2, multiplexed kinase inhibitor beads, trastuzumab, pertuzumab, lapatinib, clinical trial

Gary Johnson
contact affiliation	Department of Pharmacology, University of North Carolina Chapel Hill School of Medicine, Chapel Hill, NC USA
contact email	gary_johnson@med.unc.edu
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. PXD021865
     1. Label: PRIDE project
     2. Name: Kinome profiling in HER2+ breast cancer patients in response to 7 days of HER2-targeting