PXD005766

PXD005766 is an original dataset announced via ProteomeXchange.

Title	Proteomics to determine metallodrug targets and optimal drug combinations
Description	The FITExP profiling approach was used to identify protein hits from cells incubated with RAPTA-T or RAPTA-EA. Validation experiments with paclitaxel and cisplatin underlined the reliability of the method and hit lists for both test compounds (and?) gave physiologically viable anti-cancer mechanisms. The hit proteins for paclitaxel match with those published and the ones obtained for cisplatin were related to DNA repair, which is in line with the principal mechanism of cisplatin cytotoxicity involving the formation of nuclear DNA lesions. RAPTA-T treatment leads to upregulation of multiple hits suggesting a broad mechanism of action involving both metastasis and tumorigenicity. In contrast, hit proteins identified after incubation with RAPTA-EA are linked to regulation of the oxidative stress response and are therefore thought to be conferred by the EA moiety in the drug. From a therapeutic standpoint, RAPTA-EA could be explored in cancers where EA alone has shown potency, such as chronic lymphocytic leukemias,91 or where EA combined with another agent shows synergy, such as the combination of EA with afatinib, an irreversible epidermal growth factor receptor tyrosine kinase inhibitors for breast cancers.92 On the other hand, due to its broad mechanism of action, RAPTA-T could potentially be more useful if used concomitantly with drugs that target specific cancer pathways and could also play a role in therapies for later stage cancers due to its anti-metastatic properties. Here, application of the FITExP allowed us to gauge the mechanistic pathways involved in the action of two novel ruthenium(II) metallodrugs with very different phenotypic characteristics and from this knowledge infer their role in therapy. Potentially, future application of the FITExP approach in this manner could be useful for identification of cancer chemotherapy drug combinations, where commonly cancer clinical trials fail at phase II where drug combinations are first tried and tested.
HostingRepository	PRIDE
AnnounceDate	2018-02-09
AnnouncementXML	Submission_2018-02-09_04:35:38.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexey Chernobrovkin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2017-01-23 02:59:01	ID requested
⏵ 1	2018-02-09 04:35:39	announced

Lee RFS, Chernobrovkin A, Rutishauser D, Allardyce CS, Hacker D, Johnsson K, Zubarev RA, Dyson PJ, Expression proteomics study to determine metallodrug targets and optimal drug combinations. Sci Rep, 7(1):1590(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Cancer, FITExP, drug targets

Roman A. Zubarev
contact affiliation	Karolinska Institute, Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Scheeles väg 2, S-171 77 Stockholm, Sweden
contact email	roman.zubarev@ki.se
lab head
Alexey Chernobrovkin
contact affiliation	Karolinska Institutet, Sweden
contact email	alexey.chernobrovkin@ki.se
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/2018/02/PXD005766

PRIDE project URI

• PRIDE
  1. PXD005766
     1. Label: PRIDE project
     2. Name: Proteomics to determine metallodrug targets and optimal drug combinations