Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/198617
Title: | Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A |
Author: | Mourón, Silvana Bueno, María José Lluch, A. Manso, Luis Calvo, I. Cortes, J. Garcia Saenz, J. A. Gil Gil, M. Martinez Janez, N. Apala, J. V. Caleiras, E. Ximénez Embún, Pilar Muñoz, J. Gonzalez Cortijo, L. Murillo, R. Sánchez Bayona, Rodrigo Cejalvo, J. M. Gómez López, G. Fustero Torre, C. Sabroso Lasa, S. Malats, N. Martinez, M. Moreno, A. Megias, D. Malumbres, M. Colomer Bosch, Ramón Quintela Fandino, Miguel |
Keywords: | Càncer de mama Genòmica Medicina personalitzada Breast cancer Genomics Personalized medicine |
Issue Date: | 7-Dec-2022 |
Publisher: | Springer Science and Business Media LLC |
Abstract: | Precision oncology research is challenging outside the 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 conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N= 218) allowed the identification of 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 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-022-35065-z |
It is part of: | Nature Communications, 2022, vol. 13, num. 1, p. 7529 |
URI: | http://hdl.handle.net/2445/198617 |
Related resource: | https://doi.org/10.1038/s41467-022-35065-z |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
s41467-022-35065-z.pdf | 5.93 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License