PXD051337

PXD051337 is an original dataset announced via ProteomeXchange.

Title	An Allele Agnostic Mutant KRAS Inhibitor Demonstrates Broad Spectrum Tumour Growth Inhibition in Pancreatic Ductal Adenocarcinoma
Description	The KRAS oncogene triggers complex phosphorylation cascades, including canonical pathways such as RAF/MEK/ERK, PI3K/AKT, and RALGDS/RAL, and their engagement varies depending on the cancer context. Integration of transcriptomic, proteomic, and phosphoproteomic analysis of KRAS mutant cancers has been used to assess new therapeutic combinations, highlighting KRAS mutant cancer heterogeneity. To dissect the complexity of KRAS dependency in PDAC, we employed unbiased proteome and phosphoproteome analysis to inform on the engagement of phosphorylation cascades and define a proteomic profile of orthotopic mouse tumors with a KrasG12D mutation treated with panKRASi (BI-2493). Treatment-specific changes at phospo/proteomic level (7,134 significantly dysregulated proteins and 6,173 dysregulated phosphosites). Specifically, cell cycle regulatory CDKs are the most significantly suppressed kinases following panKRASi treatment, with a strong downregulation of cell cycle regulatory CDKs and ERK1/2. We also identified enrichment in oxidative phosphorylation and metabolic pathways and suppression of G2M checkpoint and E2F targets, coupled with a decline in DNA replication and cell cycle pathways, suggesting impairment in cell cycle progression. Together, these studies revealed robust suppression of Kras activity and cell cycle progression consistent with tumor growth inhibition and Ki67 staining under panKRASi treatment.
HostingRepository	PRIDE
AnnounceDate	2025-08-21
AnnouncementXML	Submission_2025-08-21_06:39:01.424.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Antrix Jain
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-10 07:54:25	ID requested
⏵ 1	2025-08-21 06:39:01	announced

Dataset with its publication pending

submitter keyword: KPC, panKRASi,KRAS, proteomic, phospoproteomic, PDAC

Anirban Maitra
contact affiliation	Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
contact email	amaitra@mdanderson.org
lab head
Antrix Jain
contact affiliation	Baylor College of Medicine
contact email	antrixj@bcm.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051337
     1. Label: PRIDE project
     2. Name: An Allele Agnostic Mutant KRAS Inhibitor Demonstrates Broad Spectrum Tumour Growth Inhibition in Pancreatic Ductal Adenocarcinoma