PXD033339

PXD033339 is an original dataset announced via ProteomeXchange.

Title	Targeting kinome reprogramming in ESR1 fusion-driven metastatic breast cancer
Description	Transcriptionally active ESR1 fusions promote endocrine therapy (ET)-resistant growth and metastasis of estrogen receptor-alpha positive (ERα+) breast cancer. Currently, there are no targeted treatment options for tumors harboring active fusions because the ESR1 ligand binding domain (LBD) has been replaced with non-drug binding sequences from the 3’ partner gene. A mass spectrometry (MS)-based Kinase Inhibitor Pulldown Assay (KIPA) demonstrated an increase of multiple receptor tyrosine kinases including RET in T47D cells expressing active ESR1 fusions. Integrated proteogenomics defined tumor subsets that could be responsive to RET and CDK4/6 directed therapy from 22 biologically heterogeneous ERα+ patient-derived xenograft (PDX) tumors. Inhibition of RET by repurposing an FDA-approved drug significantly suppressed ESR1 fusion-driven growth of cell, PDX-derived organoid (PDXO) and PDX models. CDK4/6 inhibitor treatment showed similar tumor reductions to RET inhibition. Here, we reveal therapeutic kinase vulnerabilities in ESR1 fusion-driven tumors, which will lay the framework for future clinical trials.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:07:33.236.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Beom-Jun Kim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-21 06:41:25	ID requested
1	2023-10-24 11:22:55	announced
⏵ 2	2023-11-14 09:07:42	announced	2023-11-14: Updated project metadata.

Gou X, Kim BJ, Anurag M, Lei JT, Young MN, Holt MV, Fandino D, Vollert CT, Singh P, Alzubi MA, Malovannaya A, Dobrolecki LE, Lewis MT, Li S, Foulds CE, Ellis MJ, Kinome Reprogramming Is a Targetable Vulnerability in ESR1 Fusion-Driven Breast Cancer. Cancer Res, 83(19):3237-3251(2023) [pubmed]

submitter keyword: breast cancer,ESR1 fusion, kinase

BEOM-JUN KIM
contact affiliation	Baylor College of Medicine
contact email	beomjunk@bcm.edu
lab head
Beom-Jun Kim
contact affiliation	Baylor College of Medicine
contact email	beomjunk@bcm.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD033339

PRIDE project URI

• PRIDE
  1. PXD033339
     1. Label: PRIDE project
     2. Name: Targeting kinome reprogramming in ESR1 fusion-driven metastatic breast cancer