PXD066316

PXD066316 is an original dataset announced via ProteomeXchange.

Title	Design of combination therapeutics from protein response to drugs in ovarian cancer cells
Description	High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecologic malignancy and novel treatment approaches are needed. Here, we used unbiased quantitative protein mass spectrometry to assess the cellular response profile to drug perturbations in ovarian cancer cells for the rational design of potential combination therapies. Analysis of the perturbation profiles revealed proteins responding across several drug perturbations (called frequently responsive below) as well as drug-specific protein responses. The frequently responsive proteins included proteins that reflected general drug resistance mechanisms such as changes in drug efflux pumps. Network analysis of drug-specific protein responses revealed known and potential novel markers of resistance, which were used to rationalize the design of anti-resistance drug pairs. We experimentally tested the anti-proliferative effects of 12 of the proposed drug combinations in 6 HGSOC cell lines. Drug combinations tested with additive or synergistic effects are plausible candidates for overcoming or preventing resistance to single agents; these include several combinations that were synergistic (with PARPi, MEKi, and SRCi). Additionally, we observed 0.05-0.11 micromolar response to GPX4 inhibitors as single agents in the OVCAR-4 cell line. We propose several drug combinations as potential therapeutic candidates in ovarian cancer, as well as GPX4 inhibitors as single agents
HostingRepository	PRIDE
AnnounceDate	2025-07-19
AnnouncementXML	Submission_2025-07-19_06:21:40.267.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabian Coscia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-18 10:18:04	ID requested
⏵ 1	2025-07-19 06:21:40	announced

Dataset with its publication pending

submitter keyword: HGSOC, Ovarian Cancer, Cell Culture, Drug Pertubation

Fabian Coscia
contact affiliation	Spatial Proteomics Lab, Max Delbrück Center for Molecular Medicine Berlin, Germany
contact email	fabia.coscia@mdc-berlin.de
lab head
Fabian Coscia
contact affiliation	Max Delbrück Center
contact email	fabian.coscia@mdc-berlin.de
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/2025/07/PXD066316

PRIDE project URI

• PRIDE
  1. PXD066316
     1. Label: PRIDE project
     2. Name: Design of combination therapeutics from protein response to drugs in ovarian cancer cells