Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/16031
Title
Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.
Author(s)
Lluch, A | Manso, L | Calvo, I | Cortes, J | Garcia-Saenz, J A | Gil-Gil, M | Martinez-Janez, N | Apala, J V | Ximénez-Embún, Pilar | Muñoz, J | Gonzalez-Cortijo, L | Murillo, R | Sánchez-Bayona, R | Cejalvo, J M | Fustero-Torre, C | Sabroso-Lasa, S | Martinez, M | Moreno, A | Colomer, R | Mouron, Silvana Andrea CNIO | Bueno Verdejo, Maria Jose CNIO | Caleiras, E CNIO | Gomez Lopez, Gonzalo CNIO | Malats, Nuria CNIO | Megias Vazquez, Diego CNIO | Malumbres Martinez, Marcos CNIO | Quintela Fandino, Miguel Angel CNIO
Date issued
2022-12-07
Citation
Nat Commun. 2022;13(1):7529.
Language
Inglés
Document type
journal article
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.
MESH
Paclitaxel | Breast Neoplasms | Humans | Female | Precision Medicine | Genomics | Cyclin-Dependent Kinase 4
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