PXD050619

PXD050619 is an original dataset announced via ProteomeXchange.

Title	KiP analysis of ER+ Breast Cancer
Description	Endocrine therapies (ET) combined with CDK4/6 inhibition (CDK4/6i) is standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however lethal drug resistance is common. Proteogenomic analyses of 22 ER+ breast cancer patient-derived xenografts (PDXs) demonstrated that PKMYT1, a WEE1 homolog, is highly estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2 independent. In clinical samples, high PKMYT1 mRNA is a resistance biomarker for both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib(RP-6306) and gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast cancer cells without functional p53 in vitro; the combination increased DNA damage and apoptosis. In palbociclib-resistant, TP53 mutant PDX organoids and xenografts, RP-6306 with low-dose gemcitabine induced greater tumor volume reduction compared to treatment with either single agent. These results demonstrate the clinical potential of RP-6306 in combination with gemcitabine for ET and CDK4/6i resistant TP53 mutant ER+ breast cancer.
HostingRepository	PRIDE
AnnounceDate	2025-05-13
AnnouncementXML	Submission_2025-05-13_06:04:31.803.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthew Holt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-14 09:07:48	ID requested
⏵ 1	2025-05-13 06:04:32	announced

10.1158/1535-7163.mct-23-0564;

Chen A, Kim BJ, Mitra A, Vollert CT, Lei JT, Fandino D, Anurag M, Holt MV, Gou X, Pilcher JB, Goetz MP, Northfelt DW, Hilsenbeck SG, Marshall CG, Hyer ML, Papp R, Yin SY, De Angelis C, Schiff R, Fuqua SAW, Ma CX, Foulds CE, Ellis MJ, PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer. Mol Cancer Ther, 23(10):1494-1510(2024) [pubmed]

submitter keyword: ER+ Breast Cancer, PKMYT1,Endocrine therapy, CDK4/6

Matthew Holt
contact affiliation	Baylor College of Medicine
contact email	mvholt@bcm.edu
lab head
Matthew Holt
contact affiliation	BCM
contact email	mvholt@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/2025/05/PXD050619

PRIDE project URI

• PRIDE
  1. PXD050619
     1. Label: PRIDE project
     2. Name: KiP analysis of ER+ Breast Cancer