PXD063024

PXD063024 is an original dataset announced via ProteomeXchange.

Title	MEK-PARP co-targeting enhances radiation response in rectal cancer.
Description	Locally advanced rectal cancer is usually treated by neoadjuvant chemoradiotherapy. However, tumor response rates to this treatment vary greatly. Thus, most patients do not reach a complete remission and have to undergo tumor resection. In the present study, we introduce a patient-derived rectal cancer organoid platform that reflects clinical radiosensitivity and use this to screen 1596 drug-radiation combinations. We identify inhibitors of RAS-MAPK signaling, especially MEK inhibitors, strongly synergizing with radiation response. Mechanistically, MEK inhibitors suppressed radiation-induced activation of RAS-MAPK signaling, and selectively downregulated the homologous recombination DNA repair pathway component RAD51, thereby achieving radio-enhancement. Through testing drug-drug-radiation combinations in organoids and cell lines, we identified synergism between PARP and MEK inhibitors to further enhance the effect of radiation. Our data support clinical testing of combined MEK and PARP inhibition with radiotherapy in locally advanced rectal cancers.
HostingRepository	PRIDE
AnnounceDate	2025-05-26
AnnouncementXML	Submission_2025-05-26_01:03:19.371.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robert Ihnatko
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral; Orbitrap Exploris 480; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-16 04:46:41	ID requested
⏵ 1	2025-05-26 01:03:19	announced

10.1101/2024.06.06.597640;

submitter keyword: proteomics, mass spectrometry,MEK-PARP co-targeting, radiation response, rectal cancer

Jeroen Krijgsveld
contact affiliation	Proteomics of Stem Cells and Cancer (B230) German Cancer Research Center (DKFZ) Heidelberg University Im Neuenheimer Feld 581 69120 Heidelberg Germany
contact email	j.krijgsveld@dkfz-heidelberg.de
lab head
Robert Ihnatko
contact affiliation	dkfz, Heidelberg
contact email	wheat-zen-whomever@duck.com
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/PXD063024

PRIDE project URI

• PRIDE
  1. PXD063024
     1. Label: PRIDE project
     2. Name: MEK-PARP co-targeting enhances radiation response in rectal cancer.