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PXD045804

PXD045804 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIdentification of strategies to overcome resistance in HER2 positive breast cancer.
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2024-01-26
AnnouncementXMLSubmission_2024-01-26_07:56:09.134.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD045804
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterConcha Gil
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-09-29 01:48:29ID requested
12024-01-26 07:56:11announced
Publication List
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]
Keyword List
submitter keyword: Breast cancer
HER2-positive
targeted therapy
trastuzumab
pertuzumab
resistance
label-free proteomics.
Contact List
Juan Madoz-Gúrpide
contact affiliationDepartment of Pathology, Fundación Jiménez Díaz University Hospital Health Research Institute (IIS—FJD, UAM)—CIBERONC, Madrid 28040, Spain.
contact emailJMadoz@fjd.es
lab head
Concha Gil
contact affiliationUCM
contact emailcai.proteomica@pas.ucm.es
dataset submitter
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Dataset FTP location
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