Lluch, AManso, LCalvo, ICortes, JGarcia-Saenz, J AGil-Gil, MMartinez-Janez, NApala, J VXiménez-Embún, PilarMuñoz, JGonzalez-Cortijo, LMurillo, RSánchez-Bayona, RCejalvo, J MFustero-Torre, CSabroso-Lasa, SMartinez, MMoreno, AColomer, RMouron, Silvana AndreaBueno Verdejo, Maria JoseCaleiras, EGomez Lopez, GonzaloMalats, NuriaMegias Vazquez, DiegoMalumbres Martinez, MarcosQuintela Fandino, Miguel Angel2023-05-092023-05-092022-12-07Nat Commun. 2022;13(1):7529.http://hdl.handle.net/20.500.12105/16031Precision 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.engSMURhttp://creativecommons.org/licenses/by-nc-sa/4.0/PaclitaxelBreast NeoplasmsHumansFemalePrecision MedicineGenomicsCyclin-Dependent Kinase 4Atribución-NoComercial-CompartirIgual 4.0 Internacional36477027131752910.1038/s41467-022-35065-z2041-1723Nature communicationsopen access