PXD016604

PXD016604 is an original dataset announced via ProteomeXchange.

Title	Optimized high-order drug mixtures improve colorectal carcinoma treatment via inactivationof MAP kinase signaling pathway and cell cycle alteration
Description	Colorectal carcinoma is currently treated with a combination of chemotherapeutic drugs supplemented with targeted drugs. Since there is an eminent need to improved therapeutic success we employed the phenotypically-driven therapeutically guided multidrug optimization (TGMO) technology to identify personalized optimal drug combinations (ODCs). Using this technology we obtained low dose synergistic and selective ODCs for a panel of human colorectal carcinoma cells that remained active in 3-dimensional heterotypic co-culture models. From RNA sequencing and phosphoproteomics analysis we noticed considerable overlap in the top 20 most active kinases in all cell lines and that the mechanism converges around MAP kinase signaling and cell cycle inhibition despite differential cell mutation status, transcript expression levels and protein kinase activity. RNA sequencing revealed differentially expressed genes that confirmed these observations. These combinations were subsequently translated to in vivo models. Interestingly, the optimized drug mixtures reduced tumor volume with 80% and significantly outperformed the standard chemotherapy (FOLFOX) in these models, while preventing toxicity, observed after FOLFOX treatment. Pharmacokinetics studies demonstrated that the combinations supported significantly enhanced drug bioavailability.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:27:07.072.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sander Piersma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-04 08:06:05	ID requested
1	2021-09-08 17:22:35	announced
⏵ 2	2024-10-22 05:27:13	announced	2024-10-22: Updated project metadata.

10.1002/1878-0261.12797;

Zoetemelk M, Ramzy GM, Rausch M, Koessler T, van Beijnum JR, Weiss A, Mieville V, Piersma SR, de Haas RR, Delucinge-Vivier C, Andres A, Toso C, Henneman AA, Ragusa S, Petrova TV, Docquier M, McKee TA, Jimenez CR, Daali Y, Griffioen AW, Rubbia-Brandt L, Dietrich PY, Nowak-Sliwinska P, Optimized low-dose combinatorial drug treatment boosts selectivity and efficacy of colorectal carcinoma treatment. Mol Oncol, 14(11):2894-2919(2020) [pubmed]

submitter keyword: Human, combination therapy,pTyr IP, single-shot , phosphoproteomics, drug selection, colorectal carcinoma, phosphokinase ranking, label-free

Connie Ramona Jimenez
contact affiliation	Amsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology, Cancer Center Amsterdam, OncoProteomics Laboratory, Amsterdam, Netherlands
contact email	c.jimenez@vumc.nl
lab head
Sander Piersma
contact affiliation	OncoProteomics Laboratory, dept of Medical Oncology, VUmc Medical Center, Amsterdam, The Netherlands
contact email	s.piersma@vumc.nl
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/2021/09/PXD016604

PRIDE project URI

• PRIDE
  1. PXD016604
     1. Label: PRIDE project
     2. Name: Optimized high-order drug mixtures improve colorectal carcinoma treatment via inactivationof MAP kinase signaling pathway and cell cycle alteration