PXD007649

PXD007649 is an original dataset announced via ProteomeXchange.

Title	Identification of new therapies for the treatment ofBRAF/NRAS wild type melanomas
Description	Despite recent therapeutic advances in the management of BRAFV600-mutant melanoma, there is still a compelling need for more effective treatments for patients who developed BRAF/NRAS wild type disease. Since the activity of single targeted agents is limited by innate and acquired resistance, we performed a high-throughput drug screen using 180 drug combinations to generate over 17,000 viability curves, with the aim of identifying agents that synergise to kill BRAF/NRAS wild type melanoma cells. From this screen we identified a promising drug combination that efficiency kills 30% of melanoma cell lines. We validated in vivo the synergy of the drug combination and found a potential marker to identify sensitive tumors. We applied a genome-wide CRISPR screening which revealed that resistance mechanisms to the drug combination. In order to investigate the mechanism of drug synergy, we treated sensitive and resistance melanoma cell lines with the single drugs and the drug combination and performed proteome analyses to investigate the changes in total proteins and protein phosphorylation. These analysis highlighted specific pathway deregulations associated to the drug synergy that allowed to get a better understanding of the drug interaction and their efficacy in killing melanoma cell lines.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:37:09.627.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Wright
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-04 07:19:44	ID requested
1	2022-05-30 07:17:03	announced
⏵ 2	2024-10-22 05:37:10	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: IMAC, Cancer,TMT

Jyoti Choudhary
contact affiliation	Wellcome Trust Sanger Institute
contact email	jc4@sanger.ac.uk
lab head
James Wright
contact affiliation	Functional Proteomics, Institute Cancer Research & Proteomic Mass Spectrometry, Wellcome Trust Sanger Institute
contact email	jw13@sanger.ac.uk
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/2022/03/PXD007649

PRIDE project URI

• PRIDE
  1. PXD007649
     1. Label: PRIDE project
     2. Name: Identification of new therapies for the treatment ofBRAF/NRAS wild type melanomas