PXD058734

PXD058734 is an original dataset announced via ProteomeXchange.

Title	Targeted KRAS(G12V) degradation elicits efficient and durable lung adenocarcinoma regression in vivo
Description	Recent drug discovery breakthroughs led to the approval of KRASG12C inhibitors in lung adenocarcinoma (LUAD). Unfortunately, clinical responses remain limited due to rapid resistance onset. Proteolysis-targeting chimeras (PROTACs) have emerged as promising alternatives to traditional inhibition. However, there is limited mechanistic understanding of KRAS degradation in vivo. Here, we developed a preclinical LUAD mouse model and demonstrated that targeted KRAS degradation induces rapid tumor regression. Transcriptional and histological analyses revealed a substantial remodeling of the tumor microenvironment. Notably, the low resistance rate observed during long-term treatment stems from proteolysis machinery dysregulation rather than KRAS absence adaptation, indicating resistance mechanisms distinct from KRAS inhibition. Our findings highlight the therapeutic potential of KRAS degradation in LUAD, offering insights into cell-intrinsic and extrinsic mechanisms driving durable antitumor responses and supporting further clinical exploration.
HostingRepository	PRIDE
AnnounceDate	2026-05-13
AnnouncementXML	Submission_2026-05-13_11:10:42.320.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marta Vilaseca
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-10 08:06:16	ID requested
⏵ 1	2026-05-13 11:10:42	announced

Dataset with its publication pending

submitter keyword: mouse models,Targeted protein degradation in vivo, resistance, lLung adenocarcinoma, KRAS, PROTACs

Marta Vilaseca
contact affiliation	Mass Spectrometry & Proteomics Core Facility (MSPCF) Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology (BIST) C/ Baldiri Reixac, 10-12 08028 Barcelona - Spain.
contact email	masspe@irbbarcelona.org
lab head
Marta Vilaseca
contact affiliation	Mass Spectrometry & Proteomics Core Facility (MSPCF) Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology (BIST) C/ Baldiri Reixac, 10-12 08028 Barcelona - Spain
contact email	masspe@irbbarcelona.org
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/2026/05/PXD058734

PRIDE project URI

• PRIDE
  1. PXD058734
     1. Label: PRIDE project
     2. Name: Targeted KRAS(G12V) degradation elicits efficient and durable lung adenocarcinoma regression in vivo