2026-06-14T03:51:19Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/160312025-05-29T18:31:15Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Lluch, A author Manso, L author Calvo, I author Cortes, J author Garcia-Saenz, J A author Gil-Gil, M author Martinez-Janez, N author Apala, J V author Ximénez-Embún, Pilar author Muñoz, J author Gonzalez-Cortijo, L author Murillo, R author Sánchez-Bayona, R author Cejalvo, J M author Fustero-Torre, C author Sabroso-Lasa, S author Martinez, M author Moreno, A author Colomer, R author Mouron, Silvana Andrea author Bueno Verdejo, Maria Jose author Caleiras, E author Gomez Lopez, Gonzalo author Malats, Nuria author Megias Vazquez, Diego author Malumbres Martinez, Marcos author Quintela Fandino, Miguel Angel author 2022-12-07 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. Nat Commun. 2022;13(1):7529. 10.1038/s41467-022-35065-z 2041-1723 Nature communications 36477027 http://hdl.handle.net/20.500.12105/16031 Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.