PXD034355-1

PXD034355 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomic analysis of neoadjuvant breast cancer reveals a subset of patients with increased sensitivity to paclitaxel driven by CDK4 and Filamin A.
Description	Precision oncology research is challenging outside contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conducted a phosphoproteomic screening in a neoadjuvant trial of HER2-negative breast cancer patients (N=130) treated with paclitaxel or paclitaxel plus nintedanib, aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 15 candidate biomarkers through 2 independent patient sets (N=218) allowed finding a subgroup of patients characterized by high levels of CDK4 and Filamin-A, who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulated Filamin-A transcription, which in turn formed a complex with Tubulin and CLIP-170, what elicited increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allowed finding explainable predictive factors for paclitaxel.
HostingRepository	PRIDE
AnnounceDate	2022-11-08
AnnouncementXML	Submission_2022-11-08_04:10:00.898.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MiguelQuintela
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-06 02:19:52	ID requested
⏵ 1	2022-11-08 04:10:01	announced

Dataset with its publication pending

submitter keyword: breast cancer, Filamin A,Phosphoproteomics, CDK4, paclitaxel

MiguelQuintela-Fandino
contact affiliation	Breast Cancer Clinical Research Unit Centro Nacional de Investigaciones Oncológicas – CNIO Madrid, Spain.
contact email	mquintela@cnio.es
lab head
MiguelQuintela
contact affiliation	Spanish National Cancer Research Centre, Spain
contact email	mquintela@cnio.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034355
     1. Label: PRIDE project
     2. Name: Phosphoproteomic analysis of neoadjuvant breast cancer reveals a subset of patients with increased sensitivity to paclitaxel driven by CDK4 and Filamin A.