biostudies-literatureMouron SNIMHD NIH HHS7529https://www.ebi.ac.uk/biostudies/studies/S-EPMC9729295biostudies-literatureUnknown13(1)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 filamiNature communicationsPhosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.PMC9729295L60 MD003733Sabroso-Lasa SQuintela-Fandino MSanchez-Bayona RFustero-Torre CManso LGarcia-Saenz JAMoreno AGomez-Lopez GMunoz JMurillo RGonzalez-Cortijo LMalats NColomer RMouron SMartinez-Janez NLluch ACalvo IMalumbres MBueno MJCaleiras EXimenez-Embun PGil-Gil MApala JVMartinez MMegias DCejalvo JMCortes JfalsePhosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.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 filami2022-01-01T00:00:00Z2022 Dec2026-05-28T00:40:16.299Z2025-02-18T23:34:42.243ZS-EPMC97292953647702710.1038/s41467-022-35065-z