PXD045804

PXD045804 is an original dataset announced via ProteomeXchange.

Title	Identification of strategies to overcome resistance in HER2 positive breast cancer.
Description	The use of trastuzumab and pertuzumab in combination with docetaxel for initial treatment of HER2-positive breast cancer patients has resulted in notable clinical benefits in comparison to docetaxel administered with trastuzumab alone. Nevertheless, although therapeutic success is evident at the outset, the majority of tumours eventually advance, rendering metastatic disease and subsequent recurrence in patients who have developed acquired resistance. There is an urgent requirement to enhance our comprehension of the mechanisms governing resistance, enabling us to develop targeted therapeutic approaches to improve efficacy. We produced four HER2-positive-derived cell lines through prolonged exposure to trastuzumab and pertuzumab, determining their resistance rates. We confirmed long-term resistance through a notable increase in colony formation capacity of the derived cells. We confirmed the molecular identity of the new cell lines using immunohistochemistry of their receptors and profiling of point mutations. We detected HER2 overexpression in all cell lines and resistance to trastuzumab and pertuzumab did not result in variations in ER, PR and HER2 receptor expression. Finally, a study using proteomics analysis confirmed a significant alteration in the abundance patterns of over 600 proteins. This has implications for various vital biological processes such as ribosome creation, mitochondrial functionality, and metabolism. These mechanisms may play a crucial role in developing resistance in HER2-positive breast cancer. We conclude that these BCCLs resistant to trastuzumab plus pertuzumab-based anti-HER2 therapy could be a useful resource to enhance comprehension of resistance acquisition mechanisms.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_07:56:09.134.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD045804
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Concha Gil
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	2023-09-29 01:48:29	ID requested
⏵ 1	2024-01-26 07:56:11	announced

10.3390/ijms25010207;

10.6019/PXD045804;

Sanz-, Á, lvarez M, Luque M, Morales-Gallego M, Crist, ó, bal I, Ram, í, rez-Merino N, Rangel Y, Izarzugaza Y, Eroles P, Albanell J, Madoz-G, ú, rpide J, Rojo F, Generation and Characterization of Trastuzumab/Pertuzumab-Resistant HER2-Positive Breast Cancer Cell Lines. Int J Mol Sci, 25(1):(2023) [pubmed]

submitter keyword: Breast cancer

HER2-positive

targeted therapy

trastuzumab

pertuzumab

resistance

label-free proteomics.

Juan Madoz-Gúrpide
contact affiliation	Department of Pathology, Fundación Jiménez Díaz University Hospital Health Research Institute (IIS—FJD, UAM)—CIBERONC, Madrid 28040, Spain.
contact email	JMadoz@fjd.es
lab head
Concha Gil
contact affiliation	UCM
contact email	cai.proteomica@pas.ucm.es
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/2024/01/PXD045804

PRIDE project URI

• PRIDE
  1. PXD045804
     1. Label: PRIDE project
     2. Name: Identification of strategies to overcome resistance in HER2 positive breast cancer.